Solid phase synthesis of a fully active analogue of cholecystokinin using the acid-stable Boc-Phe (p-CH2) SO3H as a substitute for Boc-Tyr(SO3H) in CCK8

Substitution of the -OSO₃H group in the sulfated-tyrosine by the non-hydrolyzable -CH₂SO₃H group was the first described modification of the sulfate ester that does not affect CCK₈ activity. In addition to its capacity to mimic the sulfated tyrosine residue, the amino acid Phe(p-CH₂SO₃Na) was shown to be stable in acidic media, including HF containing mixtures. The synthesis of Boc-Phe(p-CH₂SO₃Na)-OH in racemic and resolved forms and its introduction into the sequence of CCK₈ by solid phase using standard Boc/benzyl synthesis conditions and BOP as coupling reagent is now reported. The two CCK₈ analogues containing the l - or the d -Phe(p-CH₂SO₃Na) residue, obtained in satisfactory yields, were separated by HPLC and the stereochemistry of Phe(p-CH₂SO₃Na) residue in each peptide was established by NMR spectroscopy and confirmed by a separate solid phase synthesis in which the pure l isomer was used. Both CCK₈ analogues displayed high affinities for peripheral and central receptors (KI ～ 1 nm ) and proved to be full agonists in the stimulation of pancreatic amylase secretion. The ?stabilized-CCK₈ peptide”, easily prepared by solid phase, could replace the native peptide in biochemical and pharmacological studies. Moreover the modified amino acid Phe (p-CH₂SO₃Na) could also be used in solid phase synthesis to prepare a wide variety of CCK analogues and more generally, peptides analogues containing the acid-labile O-sulfated tyrosine.     

New convenient synthesis of immunostimulating peptides containingmeso-diaminopimelic acid Syntheses of FK-565 and FK-156

A new improved synthesis of two immunostimulating peptides: FK-156 (d -lactyl-alanyl-γ-d -glutamyl-(l )-meso-2,6-diaminopimelyl-(l )-glycine)and FK-565 (heptanoyl-γ-d -glutamyl-(l )-meso-2,6-diaminopimelyl-(l )-d -alanine) is described. A proper differentiation between the two chiral amino acid moieties of diaminopimelic acid was accomplished by selective enzymatic hydrolysis of one methyl ester group of the l -centre of Z₂-meso-A₂pm(OMe)₂ (2). Utilization of a commercially available protease and diester 2 as an enzyme substrate made possible the relatively simple synthesis of a key intermediate 4 and considerably simplified the final deprotection steps. Aminolysis of the N-carboxyanhydride (4) with d -AlaONBzl or GlyONBzl was chosen to obtain the appropriate dipeptides with one free amino group as convenient intermediates for further peptide synthesis. The BOP reagent, used for peptide bond formation, secured good yields and high chemical and chiral purity of the peptides. A modification of alanine deamination procedure leading to a significant increase of d -Lac(OAc) yield is presented.     

Use of 10% sulfuric acid/dioxane for removal of N-α-tertiary-butyloxycarbonyl group during solid phase peptide synthesis

The hazards and high costs associated with the use of trifluoroacetic acid (TFA) in the removal of the N-α-tertiary-butyloxycarbonyl (Boc) group during solid phase peptide synthesis prompted an examination of alternative acidolytic reagents for α-amino group deprotection. N-α-Boc-glycine and N-α-Boc-isoleucine resins as well as an N-α-Boc-peptide resin were used to test the lability to various deprotection mixtures of both the N-α-Boc resin group as well as the amino acid or peptide-O benzyl ester resin linkage. Of the combinations tried, several were found, including 10% H₂SO₄/dioxane, which gave results roughly comparable to 50% TFA/CH₂Cl₂. Several peptides, 5–10 amino acid residues in length, have been successfully synthesized using the 10% H₂SO₄/dioxane mixture and were found to be comparable in purity to the same peptides prepared using the standard TFA/CH₂Cl₂ method of N-α-Boc removal. Thus, for the peptides examined, 10% H₂SO₄dioxane was found to be an inexpensive, safe, and practical alternative reagent to the more costly and hazardous 50% TFA/CH₂Cl₂ commonly used in the deprotection step of solid phase peptide synthesis.     

Acid-labile anchoring linkages for solid phase synthesis of C-terminal asparagine peptides using the Fmoc strategy

Two acid-labile substituted benzylamine type anchoring linkages, 4-benzoxy-2,6-dimethoxybenzylamine and 2-benzoxy-4,6-dimethoxybenzylamine, for solid phase synthesis of peptide amides were prepared. The N^a-9-fluorenylmethyloxycarbonyl (Fmoc) amino acids could be easily attached to the resins with DCC/HOBt (loading 0.5–0.6 mmol/g resin). After final removal of the N^a-protecting groups, treatment with TFA (50–95%) yielded amino acid and peptide amides in high purity. As we could show for the synthesis of thymulin (FTS, pGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn), these two resins with anchoring linkages are well suited for the synthesis of C-terminal Asn peptides using protected aspartic acid derivative as starting material.     

Molecular Models for Cholecystokinin‐A Receptor

Abstract: Numerous techniques have been used to elucidate the structural basis for interaction of cholecystokinin (CCK)‐related peptides with their hormone‐binding receptor, the CCK‐A receptor (CCK‐AR), including structure‐activity relationship studies, site‐directed mutagenesis, photoaffinity‐labeling, and solution NMR analysis of both CCK peptide ligands and peptide fragments derived from the CCK‐A receptor. Different structural models have been developed for the peptide‐receptor complexes using various subsets of the available experimental data (Giragossian & Mierke 2001; Ding et al. 2002; Escrieut et al. 2002). Here, we review details of the various models and evaluate the impact of selected experimental data sets on model development.     

Fmoc/solid-phase synthesis of Tyr(P)-containing peptides through t-butyl phosphate protection

The synthesis is of Tyr(P)-containing peptides by the use of Fmoc-Tyr(PO₃Me₂)-OH in Fmoc/solid phase synthesis is complicated since, firstly, piperidine causes cleavage of the methyl group from the -Tyr(PO₃ Me₂)-residue during peptide synthesis and, secondly, harsh conditions are needed for its final cleavage. A very simple method for the synthesis of Tyr(P)-containing peptides using t-butyl phosphate protection is described. The protected phosphotyrosine derivative, Fmoc-Tyr(PO₃^tBu₂)-OH was prepared in high yield from Fmoc-Tyr-OH by a one-step procedure which employed di-t-butyl N,N-diethyl-phosphoramidite as the phosphorylation reagent. The use of this derivative in Fmoc/solid phase peptide synthesis is demonstrated by the preparation of the Tyr(P)-containing peptides, Ala-Glu-Tyr(P)-Ser-Ala and Ser-Ser-Ser-Tyr(P)-Tyr(P).     

Use of the 3-nitro-2-pyridine sulfenyl protecting group to introduce Nε-branching at lysine during solid-phase peptide synthesis I. Application to the synthesis of a peptide template containing two addressable sites

TASPs (template-assembled synthetic peptides) are generated by the covalent attachment of linear peptides to a common peptide backbone, thus generating larger synthetic peptides/proteins with prefolded structure. In this work we present a strategy for the synthesis of a heterotemplate-assembled synthetic peptide containing two addressable sites. This orthogonal protection strategy would allow the selective introduction of different peptide chains via the ε-amino functions of template lysines being protected by either fluorenylmethoxycarbonyl (Fmoc) or 3-nitro-2-pyridine sulfenyl (Npys) groups. The N^α-Boc-N^ε-Npys-l -lysine required for solid-phase peptide synthesis (SPPS) is not readily available at a reasonable cost. To facilitate the more widespread use of this reagent we have compared the two published procedures for synthesizing this protected amino acid and evaluated the suitability of the products for SPPS. Two resin-bound peptides, a tripeptide Ac-G-K-Npys)-G-resin and an octapeptide template Ac-P₁-K₂-K₃-L₄-K_s-K₆-P₇-G₈-resin, were synthesized by SPPS. The ε-amino functions of lysines K₂ & K₆ and K₃ & K₅ of the octapeptide were protected by Fmoc and Npys groups, respectively. Secondly, these peptides were used to evaluate various reagents and reaction conditions for the deprotection of the ε-amino function of lysines bearing the N_ε-Npys protecting group. A procedure for the optimized selective and quantitative deprotection of the Npys group from the ε-amino function of lysine in a resin-bound peptide using 2-mercaptopyridine-N-oxide is described. © Munksgaard 1995.     

Synthesis of α-factor analogues containing photoactivatable and labeling groups

Analogues of α-factor, the Saccharomyces cerevisiue tridecapeptide mating pheromone (H-Trp-His-Trp-Leu-Gin-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr-OH), containing both p-benzoyl phenylalanine (Bpa), a photoactivatable group, and 3-(mono- or di-iodo-4-hydroxyphenyl)propanoic acid (iodinated HPP) or biotin as a tag, were synthesized using solid-phase methodologies on a [phenylacetamidol-methyl (PAM) resin. Bpa was introduced into the peptides using Bpa-hydroxybenzotriazole active ester during peptide chain assembly. Biotinylated α-factor analogues were prepared by assembling the desired peptide on the resin, and then reacting a specific amino group either with the symmetrical anhydride of biotin or with biotin using BOP as the activating agent prior to anhydrous hydrogen fluoride cleavage. Iodinated HPP was incorporated by acylating free peptides with Bolton-Hunter reagent (3-[diiodo-4-hydroxyphenyl]propanoic acid hydroxysuccinimide ester) in N,N-dimethylformamide and borate buffer (pH 8.0) solutions. Purification of all peptides to 98% or greater homogeneity was accomplished by high-performance liquid chromatography on a reversed-phase μ-Bondapak C₁₈ column with acetonitrile/water/trifluoroacetic acid as the mobile phase. All products were characterized by amino acid analysis and fast atom bombardment mass spectrometry. Two analogues, α-(diiodotyrosine)-His-Bpa-Leu-Gln-Leu-Arg-Pro-Gly-Gln-Pro-Nle-Tyr-OH, and ε-(diiodo-HPP)-Lys-His-Bpa-Leu-Gln-Leu-Arg-Pro-Gly-Gln-Pro-Nle-Tyr-OH, were one-twentieth to one-fortieth as active as α-factor, and exhibited approximately one order of magnitude lower affinity to the α-factor receptor. The results suggest that these two analogues are α-factor agonists and that they can be used as probes of the α-factor receptor. © Munksgaard 1995.     

Synthesis of partial sequences of ribosomal proteins and their derivatization with acryloyl residues

Peptide sequences B-X-B (B = Arg and/or Lys; X = Glu or Asp) are of considerable interest because of their possible interactions with ribosomal RNA. The syntheses of various protected peptides with the sequence Ala-B-X-B-Ala (X = Glu or Ala) and [Arg]_n-Pro (n = 1–3) are described. They are carried out in solution according to the conventional peptide synthesis method. The carbobenzoxy group is used for Nα-protection and the methyl group for the protection of the terminal carboxyl group. The side chains of Lys and Glu are respectively blocked with the tert.-butyloxycarbonyl and the tertiary butyl group and the guanidinic function of arginine with the NO₂-group. The intermediate peptides are purified either by extraction or by size exclusion chromatography. A specially adapted strategy of peptide synthesis allows removal of the amino terminal Cbo-group at the end of the synthesis and introduction of an acryloyl group. By radical copolymerization with cross-linking agents these acryloyl derivatives can be transferred into insoluble peptide gels suitable for affinity chromatography and for investigating peptide-oligonucleotide interactions. The isolation of the unprotected peptides Arg-Arg-Arg-Pro, Ala-Arg-Glu-Arg-Ala, Ala-Arg-Glu-Lys-Ala, Ala-Arg-Ala-Lys-Ala, Ala-Lys-Glu-Lys-Ala and their characterization using amino acid analysis, electrophoresis, and FAB-mass spectrometry is also reported.     

Synthesis and evaluation of potential affinity labels derived from endomorphin‐2

Abstract: In an attempt to identify potential peptide‐based affinity labels for opioid receptors, endomorphin‐2 (Tyr‐Pro‐Phe‐PheNH₂), a potent and selective endogenous ligand for µ‐opioid receptors, was chosen as the parent peptide for modification. The tetrapeptide analogs were prepared using standard Fmoc‐solid phase peptide synthesis in conjunction with incorporation of Fmoc‐Phe(p‐NHAlloc) and modification of the p‐amino group. The electrophilic groups isothiocyanate and bromoacetamide were introduced into the para position on either Phe³ or Phe⁴; the corresponding free amine‐containing peptides were also prepared for comparison. The peptides bearing an affinity label group and their free amine analogs were evaluated in a radioligand‐binding assay using Chinese hamster ovary (CHO) cells expressing µ‐ and δ‐opioid receptors. Modification on Phe⁴ was better tolerated than on Phe³ for µ‐receptor binding. Among the analogs tested, [Phe(p‐NH₂)⁴]endomorphin‐2 showed the highest affinity (IC₅₀ = 37 nm ) for µ‐receptors. The Phe(p‐NHCOCH₂Br)⁴ analog displayed the highest µ‐receptor affinity (IC₅₀ = 158 nm ) among the peptides containing an affinity label group. Most of the compounds exhibited negligible binding affinity for δ‐receptors, similar to the parent peptide.     

Synthesis and binding properties of specific photoaffinity ligands for μ and δ opioid receptor subtypes

We report the synthesis and binding properties of specific photoaffinity ligands for μ and δ opioid receptor subtypes. These ligands are derived from DAGO: Tyr-D-Ala-Gly-NMePhe-Gly-ol, a μ selective probe and DTLET: Tyr-D-Thr-Gly-Phe-Leu-Thr, a δ selective probe by modifying the Phe 4 residue. These modifications are: i) a nitro group on the para position of Phe ring as Phe(4 NO₂) or Nip, ii) an azido group as Phe(4 N₃) or AZ. Pharmacological responses on mouse vas deferens (δ sites) and guinea pig ileum (μ sites), as well as competition experiments with [³H] DAGO and [³H] DTLET on crude rat brain membranes have been performed. The nitro group on the phenyl ring of the Phe residue preserves the affinity and selectivity of each probe: NipDAGO for the μ sites, NipDTLET for the δ ones. However the nitro probes do not appear to be photo-activable by u.v. irradiation. Likewise, azidation of the phenyl ring of the Phe residue does not change the receptor selectivity of each probe, but AZDAGO has less affinity than its parent molecule DAGO, while AZDTLET has more affinity than DTLET. These compounds are photoactivable and provide an efficient tool to characterize and isolate the different receptor subtypes, especially the δ site.     

Structural requirements of the oxytocin receptor in rat uterus

Published and newly calculated pA₂-values of 147 neurohypophyseal hormone analogues (7 positions varied) acting as inhibitors of oxytocin on isolated rat uterus in vitro have been subjected to fractionation according to the method by Free and Wilson which was slightly modified for this purpose. The computation was carried out in several steps. After each step, substances with outlying pA₂ -values were el minated. The reduced group containing 73–79% of the original substances displayed a high degree of additivity of side chain contributions (SCC). This group seems to follow the “participation” rule as formulated by Free and Wilson. Analysis of the group of eliminated substances and of the resulting SCC-spectrum (level diagram) enabled us to draw some conclusions concerning the structural requirements of receptor binding: i) The intact ring structure is necessary for the peptide-receptor interaction: linear peptides or peptides with an extended ring are always outliers; ii) Carba analogues (substitution with CH₂ in the disulfide ring) display better affinities than peptides with an S-S ring; d -Arg⁸ substitution decreases the binding affinity; iii) Considerably better additivity is achieved when peptides are divided into subgroups with vasopressin-like and oxytocin-like features; populations of receptors more specific for vasopressin and for oxytocin, respectively, can be assumed. Estimates of the “true” receptor-peptide dissociation constants can be obtained by summation of the corresponding SCC's in each investigated position. The value obtained for oxytocin is identical with the medium affinity binding site on myometrial cells, and not with the high affinity site. A nonlinear relationship exists between SCC's computed from pA₂-values for magnesium-free and magnesium-containing (0.5 mm ) media but no evidence speaks in favor of a Mg-potentiating effect on receptor binding.     

Insect neuropeptide antagonist. Part II. Synthesis and biological activity of backbone cyclic and precyclic PBAN antagonists

Abstract: A new approach for the design and synthesis of pheromone biosynthesis activating neuropeptide (PBAN) agonists and antagonists using the backbone cyclization and cycloscan concepts is described. Two backbone cyclic (BBC) libraries were synthesized: library I (Ser library) was based on the active C‐terminal hexapeptide sequence Tyr‐Phe‐Ser‐Pro‐Arg‐Leu‐NH₂ of PBAN1‐33NH₂; whereas library II (d ‐Phe library) was based on the sequence of the PBAN lead linear antagonist Arg‐Tyr‐Phe‐d ‐Phe‐Pro‐Arg‐Leu‐NH₂. In both libraries the Pro residue was replaced by the BBC building unit N^α‐(ω‐aminoalkyl) Gly having various lengths of alkyl chain. The peptides of the two libraries were tested for agonistic and antagonistic activity. Four precyclic peptides based on two of the BBC antagonists were also synthesized; their activity revealed that a negative charge at the N‐terminus of the peptide abolished antagonistic activity. We also describe the use of the reagent SiCl₃I for selective deprotection of the Boc group from the building unit prior to on‐resin amino‐end to backbone‐nitrogen (AE‐BN) cyclization, during solid‐phase synthesis with Fmoc chemistry.     

酪氨酸相关肽的合成及抗孕酮生成活性

利用固相法合成了二十个含羟基氨基酸的小肽。其中,以0.5mol·L^-1二甲二氯硅烷/1.5mol·L^-1苯酚/DCM*为脱除Boc试剂,以TFMSA为切除树脂试剂。经C-18反相柱纯化后,全部产物均通过氨基酸分析要求。体外黄体细胞分泌孕酮实验表明有八个肽化物GlyTyrAlaLys,(SarSer)₂Lys及其申酯,TyrLys,HisTyr-NH₂,ThrProTyrLys-NH₂,TyrThrProArgLys,AspHisProThr-PheLys显示较强的抑制hCG致孕酮分泌的活性,而且前三个肽还能显著抑制基础孕酮的分泌,相反,GlySerTyr能刺激基础孕酮的分泌。目前尚未建立合理的结构一活性关系。     

Use of triphenylmethyl (trityl) amino protecting group in the synthesis of ketomethylene analogues of peptides

The Grignard reagents of 2-(2-bromoethyl)-1,3-dioxane and 2-(2-bromoethyl)-1,3-dioxolane readily reacted with the 2-thiopyridyl ester of N-triphenylmethyl-l -leucine to give the ketone adducts 2-[3-oxo-4(S)-(triphenylmethyl) amino-6-methylheptyl]-1,3-dioxane (8a) and 2-[3-oxo-4(S)-(triphenylmethyl) amino-6-methylheptyl]-1,3-dioxolane (8b) in near quantitative yield. When 1 equiv. of the Grignard reagent of 2-(2-bromoethyl)-1,3 dioxane was used, the desired ketone adduct 8a was formed slowly but quantitatively. In contrast, when 2 equiv. of the Grignard reagent were used, the formation of ketone 8a was instantaneous. The triphenylmethyl protecting group was easily removed from 8a using dilute acid to give the amino ketone 2-[3-oxo-4(S)-amino-6-methylheptyl]-1,3-dioxane oxalate salt (9). This material served as a useful intermediate in the synthesis of the ketomethylene analogues of the peptides, Z-Pro-Leu-Gly-OH and Leu-Gly-Val-Phe-OCH₃.     

Solid phase synthesis of peptides containing the non-hydrolysable analog of (O)phosphotyrosine,P(CH2PO3H2)Phe

Studies about phosphorylation-dephosphorylation mechanisms require the development of probes capable of being used in in vitro and in vivo conditions. We show in this work that the chemically and enzymatically stable p(CH₂PO₃H₂) Phe analog of (O)phosphotyrosine can be easily introduced in peptides by the solid-phase method. It has been incorporated in the 344-357 sequence of the β₂ adrenergic receptor in place of the Tyr residue in position 350 and/or 354 in order to investigate the role of tyrosine phosphorylation in the receptor agonist-induced down-regulation. Since p(CH₂PO₃H₂)Phe is an ionized hydrophilic residue, peptides containing this amino acid do not easily permeate the cellular membranes. Therefore the modified amino acid was introduced in the synthetic pathway in its N-Boc- p (CH₂PO₃Et₂)Phe form, which could be partially or completely deprotected. Coupling steps, including that of the new amino acid, were performed with good yields (~60% total yield) and further deprotections provided both the p(CH₂PO₃H₂)Phe and p(CH₂PO₃HEt)Phe containing peptides with yields of around 20% each. The structure of the peptides was assessed by NMR, mass spectroscopy and amino acid analysis and the new amino acid was characterized under its phenyl-thiocarbamyl form (PTC).     

Cyclic peptide substrates of pp60c-src

To study the effects of constrained conformation and amino acid sequence on their kinetic parameters, a series of cyclic peptides were synthesized and each was tested as both a substrate and an inhibitor of pp60^c-src, the product of the src proto-oncogene. The amino acid sequences were derived from Glu-Leu-Pro-Tyr-Ala-Gly and from the autophosphorylation site of pp60^c-src (Ile-Glu-Asp-Asn-Glu-Tyr-Ala-Ala-Arg-Gln-Gly). Linear precursor peptides were synthesized by SPPS on aminomethylated polystyrene resin using the Fmoc-tert-butyl protection scheme with 4-hydroxymethyl-3-methoxyphenoxyacetic acid as the linkage agent. The peptides were cleaved from the support with 1% TFA in dichloromethane with the N-terminal Fmoc and the side-chain protecting groups in place. Removal of the Fmoc group with diethylamine and cyclization with BOP afforded cyclic peptides in 55–78% yield. Side-chain deprotection and further purification gave the final products in 25–48% yields based on their linear precursors. Based on the activities of the linear analogues, cyclization had little effect on the binding (K_i and K_m) and rate of phosphorylation (V_max) of cyclo(Glu-Leu-Pro-Tyr-Ala-Gly) and cyclo(Ile-Glu-Asp-Am-Glu-Tyr-Ala-Ala-Arg-Gln). A series of cyclic decapeptides that contained the dipeptide d -Phe-Pro inserted in various positions in the autophosphorylation sequence showed marked differences in K_i, K_m and V_max. Compared to the well characterized linear substrate Val-5 angiotensin II, the D-Phe-Pro-containing cyclic peptides have higher V_max values but differ little in K_m, with values in the millimolar range.     

Application of arylsulphonyl side-chain protected arginines in solid-phase peptide synthesis based on 9- fluorenylmethoxycarbonyl amino protecting strategy

One of the main problems still hampering solid-phase peptide synthesis using orthogonal protection strategies based on the 9-fluorenylmethoxycarbonyl amino protecting group is the difficult removal of currently used arginine arylsulphonyl guanidino protecting groups. Poor acid lability of 4-methoxy-2,3,6-trimethylbenzenesulphonyl-protected arginine has led to the popularity of the newer 2,2,5,7,8-pentamethylchroman-6-sulphonyl guanidino protecting group. This group was initially believed to have lability to trifluoroacetic acid, the reagent commonly used to simultaneously deprotect peptides and detach them from the synthesis resin, comparable to tert.-butyl and trityl type protecting groups used for the protection of other peptide side-chain functionalities. In a comparison of three established cleavage/deprotection mixtures we have shown that this is not always the case, particularly in multiple arginine peptides. We have found that only hard-acid deprotection with trimethylsilyl bromide reliably removed both arylsulphonyl guanidino protecting groups from a variety of arginine-containing peptides.     

Cyclic hexapeptide NK-2 antagonists

The synthesis of 11 cyclic hexapeptides, some of which contain a carbohydrate side chain moiety, is described in this paper. A glycosylamine was coupled without hydroxyl protecting groups either directly or via a butyric acid spacer to the side chain of glutamic acid, leading to β-N-glycosylated peptides. All peptides described are selective NK-2 antagonists. The binding affinity to the NK-2 receptor ranges from 7 × 10^?7 to 1 × 10^?8 M, whereas at the NK-I receptor the IC₅₀ was > 10^?5 M with the exception of cyclo(-Lys(Boc)-Trp-Phe-Gly-Leu-D-Leu-) (I), which shows low affinity to the NK-1 receptor (IC₅₀= 9 × 10^?6 M). The antagonist activity is determined in the hamster trachea assay. pA₂-Values range from 7.1 to 7.8. The results demonstrate the broad range of side chains which can be accommodated at the glutarnine position without a major drop in activity. The different charges of the lysine and the glutamic acid peptides indicate that the interaction with the receptor at this position is not determined by ionic forces. Rather, we expect that conformational flexibility allows differently charged amino acid residues to be accommodated by the receptor.     

Solid-phase synthesis of oxytocin using iodotrichlorosilane as Boc deprotecting agent

Deprotection of the tert-butoxycarbonyl group during solid-phase synthesis of peptides can be conveniently and efficiently carried out using a neutral reagent, silicon tetrachloride/sodium iodide (iodotrichlorosilane). This simple and rapid method has been advantageously employed during the solid-phase synthesis of the pituitary hormone, oxytocin.