共查询到20条相似文献,搜索用时 15 毫秒
1.
NMR spectroscopy has been employed for the conformational analysis of the cyclic hexapeptide cycle(-d -Pro1-Ala2-Ser3(Bzl)-Trp4-Orn5(Z)-Tyr6-) with and without protecting groups on Ser3 and Orn5. This peptide sequence was derived from the active loop sequence of the α-amylase inhibitor Tendamistat (HOE 467). The aim was to investigate the role of serine in position i of a standard β-turn on the conformation and stabilization of this turn. Based on distance and torsion constraints from 2D NMR spectroscopic measurements in DMSO-d6 solution, structure refinement was accomplished by restrained molecular dynamics (MD) simulations in vacuo and in DMSO. The analysis of both structures in solution reveals a considerable effect of the unprotected serine sidechain on the adjacent β-turn conformation. While in the protected peptide with Ser3(Bzl) a βII-turn is observed between Trp4 and Orn5, the deprotected compound reveals a βI-turn in this region. The βI-turn is stabilized by a backbone-sidechain hydrogen bond from Orn5NαH to Ser3Oγ. Comparisons with other NMR-derived solution structures of cyclic model peptides and in some protein structures from literature reveal a general structural motif in the stabilization of βI-turns by serine in the i position through backbone-sidechain interactions. © Munksgaard 1995. 相似文献
2.
U. WOLLBORN R.M. BRUNNE J. HARTING G. H
LZEMANN D. LEIBFRITZ 《Chemical biology & drug design》1993,41(4):376-384
The conformational analysis of three cyclic hexapeptides is presented. Cyclo-(-Gln6-Trp7-Phe8-Gly9-Leu10-d -Met11-) (1) and cyclo-(-Gln6-Trp7-Phe8-Gly9-Leu10-Met11-) (2) are NK-2 antagonists in the hamster trachea assay, whereas cyclo-(-Gln6-Trp7-Phe8-(R)-Gly9-[ANC-2]Leu10-Met11-) (3), where Gly9[ANC-2]Leu10 represents (2S)-2-((3R)-3-amino-2-oxo-1-pyrrolidinyl)-4-methylpentanoyl, is inactive as agonist and antagonist in this assay. In DMSO, the NMR results cannot be interpreted as being consistent with a single conformation. However, the combined interpretation of results from NMR spectroscopy, restrained molecular dynamics simulations with application of proton–proton distance information from ROESY spectra, and pharmacological results leads to a reduced number of conformational domains for each peptide, which can be compared with each other and may be classified as responsible for their biological activity. Trying to match the conformational domains approximately with regular β- and γ-turns, we find a γn-turn at the position of the methionine occuring in all peptides. For the active peptides 1 and 2 we arrive at an inverse γi-turn at Phe8, and βI′- or βII-turns with Gly9 and Leu10 at the corner positions, these β-turns having a similar topology with respect to the linking peptide unit. Other conformational domains common to only 1 and 2 support their classification as responsible for the biological activity. 相似文献
3.
H. KESSLER H. MATTER G. GEMMECKER H.-J. DIEHL C. ISERNIA S. MRONGA 《Chemical biology & drug design》1994,43(1):47-61
Synthesis and conformational analysis of three cyclic hexapeptides cyclo(-Gly1-Pro2-Phe3-Val4-Xra5-Phe6), Xaa= Phe (I), D-Phe (II) and D-Pro (III), were carried out to examine the influence of proline on the formation of reverse turns and the dynamics of hydrophobic peptide regions. Assignment of all 1H and 13C resonances was achieved by homo- and heteronuclear 2D-NMR techniques (TOCSY, ROESY, HMQC, HMQC-TOCSY and HMBCS-270). The conformational analysis is based on interproton distances derived from ROESY spectra and homo- and heteronuclear coupling constants (E.COSY, HETLOC and HMBCS-270). For structural refinements restrained molecular dynamics (MD) simulations in vacuo and in DMSO were performed. Each peptide exhibits two conformations in DMSO solution due to cis-trans isomerism about the Gly-Pro peptide bond. Surprisingly the cis-Gly-Pro segment in the minor isomers is not involved in a βVI-turn, but forms a turn structure with cis-Gly-Pro in the i and i+ 1 positions. Although no stabilizing hydrogen bond is found in this turn, the φ and ψ-angles closely correspond to a βI-turn [Pro2:φ(i+ 1) -60°, ψ(i+ 1) -30° Phe3: φ(i+ 2) -100°, ψ(i+ 2) -50°]. Hence we call this structural element a pseudo-βI-turn. As expected, in the dominating all-trans isomers proline occupies the i+ 1 position of a standard βI-turn. Therefore, cis-trans isomerization of the Gly1-Pro2 amide bond only induces a local conformational rearrangement, with minor structural changes in other parts of the molecule. However, the geometry of the other regions is affected by the chirality of the i+ 1 amino acid for both isomers (βI for Phe5, βII′ for D-Phe5 or D-Prp5). 相似文献
4.
HORST KESSLER ARMIN GEYER HANS MATTER MATTHIAS KOCK 《Chemical biology & drug design》1992,40(1):25-40
One carbonyl oxygen of the cyclic hexapeptide cycle(-Gly1-Pro2-Phe3-Val4-Phe5-Phe6-) (A) can be selectively exchanged with sulphur using Yokoyama's reagent. Surprisingly it was not the C=O of Gly1 but that of Phe5 which was substituted and cyclo(-Gly1-Pro62-Phe3-Va14-Phe5ψ[CS-NH]Phe6-) (B)was obtained. Thionation results in a conformational change of the peptide backbone although the C=O of Phe5 and the corresponding C=S are not involved in internal hydrogen bonds. Two isomers in slow exchange, containing a CIS Gly1-Pro2 bond in a βVIa-turn (minor) and a trans Gly-Pro bond in a βII′-turn (major), were analyzed by restrained molecular dynamics in vacuo and in DMSO as well as using time dependent distance constraints. It is impossible to fit all experimental data to a static structure of each isomer. Interpreting the conflicting NOES, local segment flexibility is found. MD simulations lead to a dynamic model for each structure with evidence of an equilibrium between a βI- and βII-turn about the Val4-Phe5 amide bond in both the cis and trans isomers. Additionally proton relaxation rates in the rotating frame (R1p) were measured to verify the assumption of this fast βI/βII equilibrium within each isomer. Significant contributions to R1p-rates from intramolecular motions were found for both isomers. Therefore it is possible to distinguish between at least four conformers interconverting on different time scales based on NMR data and MD refinement. This work shows that thionation is a useful modification of peptides for conformation-activity investigations. 相似文献
5.
Using a data set of 250 non-homologous high-resolution globular proteins, a systematic analysis of the conformations that precede and succeed (positions i and i+3) the various classical β-turn types has been carried out. The collective conformation of a specific β-turn type, including the flanking positions, termed motif, has been studied. In all the four turn types, the majority of examples are preceded and succeeded by extended conformation. Some of the other observations are: (1) In a type I β-turn, Gly at position i+ 3 has a higher favorability to occur with positive ø and does not prefer the major motif βαR-αR-β. (2) The left-handed alpha;-helical conformation (alpha;L) is not preferred at both the flanking positions for type I'and II β-turns, (3) The β–β motif is favourable for all the turn types and the motif β–αL very highly favourable for type I. © Munksgaard 1996. 相似文献
6.
G.V. NIKIFOROVICH O.M. PRAKASH CATHERINE A. GEHRIG VICTOR J. HRUBY 《Chemical biology & drug design》1993,41(4):347-361
The solution structures of DPDPE, a conformationally restricted pentapeptide with the sequence H-Tyr1-d -Pen2-Gly3-Phe4-d -Pen5-OH, and its four β-MePhe4-substituted analogs were examined by a combined approach including the NMR measurements in DMSO and water as well as independent energy calculations. It was concluded that several low energy conformers of DPDPE backbone satisfy the NMR data obtained in this study as well as in previous studies by other authors. These possible solution conformers of DPDPE in both DMSO and water share virtually the same type of cyclic backbone structure, with the Gly3 residue in a conformation close to a γ-turn, and the Phe4 residue in a conformation close to α-helical torsion angles. They differ in the space arrangements of the flexible Tyr1 moiety. The solution structures of the β-MePhe4-substituted analogs of DPDPE are interesting. For analogs with an S-configuration at the Cα atom in the Phe4 residue, the cyclic backbone conformations resemble those of DPDPE itself, whereas for analogs with an R-configuration at the Cα atom, the backbone conformation is somewhat different. This observation is in line with the high biological potencies and selectivities displayed by the former compounds but not by the latter ones. It was noted also that as far as the peptide backbone conformers are concerned, some of the possible DPDPE conformers in water are similar to the previously suggested model for the δ-receptor-bound conformation of DPDPE, becoming virtually identical to this conformation by rotating the side chains of the Tyr1 and the Phe4 residues. 相似文献
7.
MAMATA S. PRACHAND M. M. DHINGRA ANIL SARAN EVANS COUTINHO J. BODI H. SÜLI-VARGHA K. MEDZIHARDSZKY 《Chemical biology & drug design》1998,51(4):251-265
Solution conformation of cyclo(Gly1-His2-Phe3-Arg4-Trp5-Gly6) and its d -Phe analog corresponding to the message sequence [Gly-α-MSH5-10] of α-MSH has been studied by 1D and 2D proton magnetic resonance spectroscopy in dimethyl sulfoxide (DMSO)-d6 solution and in a DMSO-d6/H2O cryoprotective mixture. The NMR data for both the analogs in solution at 300 K cannot be interpreted based on a single ordered conformation, as evidenced by the broadening of only -NH resonances as well as the temperature coefficients of the amide protons. An analysis of the nuclear Overhauser effect (NOE) cross-peaks in conjunction with temperature coefficient data indicates an equilibrium of multiple conformers with a substantial population of particular conformational states at least in the d -analog. The molecular dynamics simulations without and with NOE constraints also reveal numerous low-energy conformers with two γ-turns, a γ-turn and a β-turn, two β-turns, etc. for both the analogs. The observed NMR spectra can be rationalized by a dynamic equilibrium of conformers characterized by a γ-bend at Gly6, two γ-bends at Phe3 and Gly6 and a conformer with a single β-turn and a γ-bend for the l -Phe analog. On the other hand, a conformation with two fused β-turns around the two tetrads His2-d -Phe3-Arg4-Trp5 and Trp5-Gly6-Gly1-His2 dominates the equilibrium mixture for the d -Phe analog. For the d -Phe analog, the experimentally observed average conformation is corroborated by molecular dynamics simulations as well as by studies in cryoprotective solvent. 相似文献
8.
F. FILIRA L. BIONDI F. CAVAGGION B. SCOLARO R. ROCCHI 《Chemical biology & drug design》1990,36(1):86-96
Synthesis is described of four tuftsin derivatives containing a D-ghcopyranosyl or a D-galactopyranosyl unit covalently linked to the hydroxy side chain function of the threonine residue through either an α or βO-glycosidic linkage. Fmoc-threonine derivatives containing the suitable unprotected sugar were used for incorporating the O-glycosylated amino acid residue. Z-Thr[α-Glc(OBzl)4]-OBzl and Z-Thr[α-Gal(OBzl)4]-OBzl were prepared from the tetra-O-benzylated sugar and Z-Thr-OBzl by the trichloroacetimidate method in the presence of trimethylsilyl trifluoromethane sulfonate. The α glycosylated threonine derivatives were converted into Fmoc-Thr(α-G1c)-OH and Fmoc-Thr(α-Gal)-OH by catalytic hydrogenation followed by acylation with Fmoc-OSu. β-Glucosylation and β-galactosylation of threonine were carried out by reacting the proper per-O-acetylated sugar with Z-Thr-OBzl and boron trifluoride ethyl etherate in dichloromethane. Catalytic hydrogenation of the β-O-glycosylated threonine derivatives followed by acylation with Fmoc-OSu and deacetylation with methanolic hydrazine yielded Fmoc-Thr(β-Glc)-OH and Fmoc-Thr(β-Gal)-OH, respectively. The O-glycosylated threonine derivatives were then reacted with H-Lys(Z)-Pro-Arg(NO2)-OBzl in the presence of DCC and HOBt and the resulting glycosylated tuftsin derivatives were fully deblocked by catalytic hydrogenation, purified by HPLC, and characterized by optical rotation, amino acid analysis, and 1H NMR. The β-galactosylated tuftsin was also prepared by the continuous flow solid phase procedure. 相似文献
9.
ISABEL HARO JOSEP LLUÍS TORRES GREGORIO VALENCIA JOS MARÍA GARCÍA-ANT
N FRANCISCA REIG 《Chemical biology & drug design》1989,33(5):335-339
The synthesis of the hexapeptide [Glu6]SP6-11 and its glycosylated analogue at the Glu6γ-carboxyl position by solution procedures according to several strategies is discussed. The biological activity of SP, [GIu6]SP6-11 (VI) and [Glu(β-d -Glcp)6]SP6-11 (VIII) have been determined and compared to SP by the GPI and RVD assays. The introduction of a β-d -glucopyranosyl moiety at the sixth position of the [Glu6]SP6-11 did not affect to a great extent the in vitro activity pattern of the parent hexapeptide. 相似文献
10.
J. Satyanarayana T.L. Gururaja G.A. Naganagowda N. Ramasubbu M.J. Levine 《Chemical biology & drug design》1998,52(3):165-179
A facile strategy for the stereoselective synthesis of suitably protected O-glycosylated amino acid building blocks, namely, Nα-Fmoc-Ser-[Ac4-β-d -Gal-(1-3)-Ac2α or β-d -GalN3]-OPfp and Nα-Fmoc-Thr-[Ac4-β-d -Gal-(1-3)-Ac2-α or β-d -GalN3]-OPfp is described. What is new and novel in this report is that Koenigs-Knorr type glycosylation of an aglycon serine/threonine derivative (i.e. Nα-Fmoc-Ser-OPfp or Nα-Fmoc-Thr-OPfp) with protected β-d -Gal(1-3)-d -GalN3 synthon mediated by silver salts resulted in only α-and/or β-isomers in excellent yields under two different reaction conditions. The subtle differences in stereoselectivity were demonstrated clearly when glycosylation was carried out using only AgClO4 at -40°C which afforded α-isomer in a quantitative yield (α:β= 5:1). On the other hand, the β-isomer was formed exclusively when the reaction was performed in the presence of Ag2CO3AgClO4 at room temperature. A complete assignment of 1H resonances to individual sugar ring protons and the characteristic anomeric α-1H and β-1H in Ac4Galβ(1-3)Ac2GalN3α and/or β linked to Ser/Thr building blocks was accomplished unequivocally by two-dimensional double-quantum filtered correlated spectroscopy and nuclear Overhauser enhancement and exchange spectroscopy NMR experiments. An unambiguous structural characterization and documentation of chemical shifts, including the coupling constants for all the protons of the aforementioned a- and p-isomers of the O-glycosylated amino acid building blocks carrying protected β-d -Gal(1-3)-d -GalN3, could serve as a template in elucidating the three-dimensional structure of glycoproteins. The synthetic utility of the building blocks and versatility of the strategy was exemplified in the construction of human salivary mucin (MUC7)-derived, O-linked glycopeptides with varied degrees of glycosylation by solid-phase Fmoc chemistry. Fmoc/tert-butyl-based protecting groups were used for the peptidic 相似文献
11.
PAUL M. DOYLE JOHN C. HARRIS CLAIRE M. MOODY PETER J. SADLER MARTIN SIMS JANET M. THORNTON JULIA UPPENBRINK JOHN H. VILES 《Chemical biology & drug design》1996,47(6):427-436
The solution structure of cyclo-[Gly-Leu-Asp-Val-BTD] (BTD=β-turn dipeptide) has been determined by two-dimensional 1H-NMR (nuclear magnetic resonance) spectroscopy and systematic conformational searching combined with molecular dynamics studies. The structure contains two hydrogen bonds between the Gly and Val residues, and a type I β-turn with Leu and Asp at the (i+ 1) and (i+ 2) positions of the turn. The cyclic compound shows activity in a scintillation proximity assay (SPA) for the inhibition of the interaction between the integrin α4β1 and vascular cell adhesion molecule-1 (VCAM-1). The structure-activity relationship of the LDV sequence is discussed. © Munksgaard 1996. 相似文献
12.
Six cyclic retro-analogues of the peptide hormone somatostatin have been synthesized using the solid phase technique. The peptides cyclo(-Xaa1-Phe2-Thr3-Lys4-Ybb5-Phe6-) and cyclo(-Phe1-Xaa2-Thr3-Lys4-Ybb5-Phe6-) with Xaa =d - or l -Pro and Ybb =d - or l -Trp were cyclized via the azide method. The conformations of the cyclic hexapeptides in DMSO-d6 solution were determined by a number of homo- and heteronuclear two-dimensional n.m.r.-techniques including 2D rotating frame NOE-spectroscopy. Two-step coherence transfers, ROE and chemical exchange, are observed for the first time in ROESY spectra. The backbone conformation of the all-trans cyclopeptides consists of a β-turn containing the Pro residue in the position i + 1. These retro-analogues of somatostatin exhibit a high activity in the inhibition of cholate and phalloidin uptake by liver cells (cytoprotective effect); however, the hormonal activities of the natural hormone are completely suppressed. The constitutional and conformational requirements for the cytoprotective activity are discussed. 相似文献
13.
ROBERT E. LONDON PAUL G. SCHMIDT RAYMOND J. VAVREK JOHN M. STEWART 《Chemical biology & drug design》1982,19(4):334-342
Substitution of Pro residues with AIB (α-aminoisobutyric acid) residues in peptides provides a means of evaluating the presence of cis' proline conformations both in solution and, using bioassay data, in a receptor complex. 1 H n.m.r. has been used to probe the DMSO solution conformation of all seven of the possible AIB/Pro isomers of bradykinin. AIB substitution for Pro2 and/or Pro3 appears to stabilize a type III β-turn involving the N-terminal residues, but not an incipient 310 helix suggested by model peptides. These substitutions are correlated with low biological potencies, suggesting that such conformational features may be incompatible with receptor complexation. Alternatively, AIB7 -bradykinin analogs exhibit a variety of long range shift perturbations relative to bradykinin. The data suggests that bradykinin can adopt several folded conformations, including β-turns involving both Ser6-Pro7-Phe8-Arg9 and Phe5-Ser6-Pro7-Phe8. The relatively high biological activities of the AIB7-BK suggest that the complexed form of the peptide is characterized by a cis' Pro7 conformation. 相似文献
14.
The dehydro-peptide Boc-L-Ile-ΔPhe-L-Trp-OCH3 was synthesized by the azlactone method in the solution phase. The peptide was crystallized from methanol in an orthorhombic space group P212121 with a = 10.777(2), b= 11.224(2), c= 26.627(10) Å. The structure was determined by direct methods and refined to an R value of 0.069 for 3093 observed reflections [l≥ 2σ(l)].The peptide failed to adopt a folded conformation with backbone torsion angles: φ1, = 90.8(8)°, ψ1= -151.6(6)°, φ2= 89.0(8)°, ψ2= 15.9(9)°, φ3= 165.7(7)°, ψT3= -166.0(7)°. A general rule derived from earlier studies indicates that a three-peptide unit sequence with a ΔPhe at the (i+ 2) position adopts a β-turn II conformation. Because the branched β-carbon residues such as valine and isoleucine have strong conformational preferences, they combine with the ΔPhe residue differently to generate a unique set of conformations in such peptides. The presence of β-branched residues simultaneously at both (i+ 1) and (i+ 3) positions induces unfolded conformations in tetrapeptides, but a β-branched residue substituted only at (i+ 3) positron can not prevent the formation of a folded β-turn II conformation. On the other hand, the present structure shows that a β-branched residue substituted at the (i+ 1) position prevents the formation of a β-turn II conformation. These observations indicate that a β-branched residue at the (i+ 1) position prevents a folded conformation whereas it cannot generate the same degree of effect from the (i+ 3) position. This may be because of the trans disposition of the planar ΔPhe side-chain with respect to the C=O group in the residue. The molecules are packed in an anti-parallel manner to generate N2-H2…O2 (-x,y-1/2, -z+ 3/2) and Nε13-Hε13…O1(-x,y -1/2, -z+ 3/2) hydrogen bonds. 相似文献
15.
Stereochemical constraints have been introduced into the enkephalin backbone by substituting α-aminoisobutyryl (Aib) residues at positions 2 and 3, instead of Gly. 1H n.m.r. studies of Tyr-Aib-Gly-Phe-Met-NH2, Tyr-Aib-Aib-Phe-Met-NH2 and Tyr-Gly-Aib-Phe-Met-NH2 demonstrate the occurrence of folded, intramolecularly hydrogen bonded structures in organic solvents. Similar conformations are also favoured in the corresponding t-butyloxycarbonyl protected tetrapeptides, which lack the Tyr residue. A β-turn centred at positions 2 and 3 is proposed for the Aib2-Gly3analog. In the Gly2-Aib3analog, the β-turn has Aib3-Phe4as the corner residues. The Aib2-Aib3analog adopts a consecutive β-turn or 310 helical conformation. High in vivo biological activity is observed for the Aib2and Aib2-Aib3analogs, while the Aib3peptide is significantly less active. 相似文献
16.
IGNACY Z. SIEMION ALEKSANDRA KUBIK MAREK LISOWSKI ZBIGNIEW SZEWCZUK MICHAL ZIMECKI ZBIGNIEW WIECZOREK 《Chemical biology & drug design》1991,38(1):54-61
It was found that substitution of Val2 and/or Leu4 residue in a hexapeptide Tyr-Val-Pro-Leu-Phe-Pro (I) transforms this peptide immunostimulant into analogues possessing the immunosuppressor activity – Tyr-Gly-Pro-Leu-Phe-Pro (II), Tyr-Val-Pro-Gly-Phe-Pro (III), and Tyr-Gly-Pro-Gly-Phe-Pro (IV). Biological effects of peptides I-IV were studied using PFC (plaque forming cell) test, GvH (graft vs host) reaction in mice, and ARFC (autologous rosette forming cell) test. The strongest immunosuppressor activity was observed for III – in this case the immunosuppressor effect was observed even in PFC test in vitro in which II and IV showed no such activity. These results suggest that simultaneous presence of both Val2 and Leu4 residues is necessary for the generation of immunostimulation. The CD study of I-IV in methanol solution suggests that the conformational preferences of II-IV change towards stabilization of the β-turn structure, whereas in the case of I the γ-turn on Leu4 and cis orientation of the Pro3 carbonyl (distorted β-turn of type I) was found (1) as the preferred conformation. Competition in biological effects observed for I and III in PFC in vitro test suggests that these analogues may interact with the same cellular receptor. Drastic changes in the activity which accompany changes in the sequence are discussed in the terms of our stereochemical hypothesis (1). 相似文献
17.
PAUL W. BAURES WILLIAM H. OJALA WILLIAM B. GLEASON RODNEY L. JOHNSON 《Chemical biology & drug design》1997,50(1):1-13
The effect of replacing one of the proline residues in either unsubstituted homochiral or heterochiral diproline segments with either a 2- or a 3-substituted prolyl residue on the allowed conformation of the diproline template has been examined. In heterochiral (l-d ) diprolines, placement of a 2-methyl-d -proline residue in the i+ 2 position and placement of either a cis- or trans-3-methyl-l -proline residue in the i+ 1 position results in substituted diproline peptides that adopt the same type II β-turn conformation as that identified experimentally for the unsubstituted diproline peptides. In contrast, placement of a cis-3-methyl-d -proline residue in the i+ 1 position of a homochiral (d-d ) diproline peptide seems to promote a different conformation than that seen in the unsubstituted case, whereas the trans-3-methyl-d -proline residue seems to provide a stabilizing influence for the predicted type VI'β-turn. The demonstrated ability of certain substituted diproline templates to adopt predictable conformations coupled with the development of asymmetric synthetic routes to both 2- and 3-substituted prolyl residues capable of mimicking a variety of side chains should make these templates useful tools in designing specific turn mimics of biologically active molecules. 相似文献
18.
L. BIONDI F. FILIRA R. ROCCHI E. TZEHOVAL M. FRIDKIN 《Chemical biology & drug design》1993,41(1):43-51
Syntheses are described of the Hyp3-tuftsin analogue and of its derivatives α- or β-O-glycosylated at the side chain function of the hydroxyproline residue. The carbohydrate-free tetrapeptide was prepared by reacting Z-Thr-Lys(Z)-OH with H-Hyp-Arg(NO2)-OBzl by the mixed anhydride procedure. In the synthesis of the α-glycosylated analogue the O-glycosyl amino acid was incorporated by reacting Boc-(Glcα+β)Hyp-OH with H-Arg(NO2)-OBzl through the same procedure. The α-glucosylated dipeptide was isolated from the diastereomeric mixture, selectively deblocked, and acylated with Z-Thr-Lys(Z)-OH by the mixed anhydride procedure. In the preparation of the β-glucosylated analogue the BOP procedure was used for reacting Boc-[Glc(Ac)4β]Hyp-OH with H-Arg(NO)2-OBzl was well as for the final coupling to tetrapeptide. Removal of protecting groups from crude tetrapeptides was achieved by catalytic hydrogenation. Deacetylation of the sugar moiety of the β-glucosylated tetrapeptide was achieved by treatment with sodium methoxide in methanol. The synthetic compounds were isolated by ion exchange chromatography, and characterized by elemental analysis, amino acid analysis, optical rotation and proton NMR. Their capacity to evoke the release of interleukin 1 from mouse peritoneal macrophages and to modulate immunogenic activity of antigen-fed cells was evaluated, in comparison with tuftsin and rigin. All of the analogues were found to possess tuftsin-like activity. 相似文献
19.
YU-SEN WANG TOMAS G. KEMPE ASHOK K. RAINA PAUL H. MAZZOCCHI 《Chemical biology & drug design》1994,43(3):277-283
The solution conformation of a biologically active C-terminal hexapeptide analog of the pheromone biosynthesis activating neuropeptide Tyr-d -Phe-Ser-Pro-Arg-Leu-NH2 has been studied by NMR spectroscopy. A β-turn conformation was identified from the NOE connectivities observed for the peptide in a mixed solvent of water and DMSO, indicating that this is the biologically active conformation of the peptide. This study also suggests that the use of such an aqueous-like solvent mixture allows the observation of a preferred conformation for small linear peptides in the presence of conformational averaging. 相似文献
20.
CD-n.m.r. study of the solution conformation of bradykinin analogs containing α-aminoisobutyric acid
JOHN R. CANN ROBERT E. LONDON CLIFFORD J. UNKEFER RAYMOND J. VAVREK JOHN M. STEWART 《Chemical biology & drug design》1987,29(4):486-496
The conformation in aqueous solution of several α-aminoisobutyric acid (AIB)-containing analogs of bradykinin (BK) has been probed by complementary CD and 1H n.m.r. measurements. The conclusion reached is that substitution of AIB for Pro2 and/or Pro3 in BK stabilizes a degree of β-turn conformation in the N-terminal tetrapeptide moiety of the resulting analogs. Changing the solvent from water to DMSO or TFE further enhances the contribution of particular hydrogen bonded structures to the time-averaged conformation of these peptides. Bradykinin and [AIB7]-BK adopt similar hydrogen bonded conformations in TFE, apparently with a contribution from a β-turn involving their common Arg1-Pro2-Pro3-Gly4 moiety. The contrasting biological activities of BK and its AIB-analogs are considered in terms of the conformational analogy between the AIB-residue and cis1 Pro and the propensity for a β-turn at the N-terminus of the peptide. 相似文献