Fibrin clot structure and fibrinolysis in hypothyroid individuals: the effects of normalising thyroid hormone levels

See also Hemker HC, Kerdelo S, Kremers RMW. Is there value in kinetic modeling of thrombin generation? No (unless…). This issue, pp 1470–7.     

NMR and quenched molecular dynamics studies of superpotent linear and cyclic α-melanotropins

Conformational searching, computer simulations, synthesis and NMR are used on a variety of α melanocyte-stimulating hormone (α-MSH) analogues to understand the physical characteristics required for biological potency. Peptides I (AC-[Nle⁴,Asp⁵,d -Phe⁷,Lys¹⁰]α-MSH(4-10)-NH₂), II (Ac-c[Nle⁴,Asp⁵,d -Phe⁷,Lys¹⁰]α-MSH(4-10)-NH₂) and III (Ac-[Nle⁴,Asp⁵,d -Phe⁷,Dap¹⁰]α-MSH(4-10)-NH₂ all show very similar conformational properties (backbone and side-chain torsional angles), and all display high biological potencies. The modeling results for these compounds are supported by the NMR data. Peptide IV (Ac-c[Nle⁴,Asp⁵,d -Phe⁷,Dap¹⁰]α-MSH(4-10)-NH₂) appears to have a markedly different conformation and has decreased biological potency.     

Congenital Yellow Nail Syndrome: A Case Report and Its Relationship to Nonimmune Fetal Hydrops

Abstract: Yellow nail syndrome (YNS) is an uncommon disorder characterized by a triad of nail dystrophy, lymphedema, and pleural effusion. It is rare in children and congenital occurrence of YNS has been very rarely described. We report a 2‐year‐old Arab boy having congenital yellow nail syndrome with mild facial dysmorphism and bilateral conjunctival pigmentation born to consanguineous parents. One of his older siblings had died of nonimmune fetal hydrops (NIFH). The case supports the genetic basis of yellow nail syndrome with a possible relationship to nonimmune fetal hydrops.     

Synthesis of β and γ-fluorenylmethyl esters of respectively Nα-Boc-L-aspartic acid and Nα-Boc-L-glutamic acid

The orthogonal synthesis of N^x-Boc-L-aspartic acid-γ-fluorenylmethyl ester and N^α-Boc-L-glutamic acid-δ-fluorenylmethyl ester is reported. This is a four-step synthesis that relies on the selective esterification of the side-chain carboxyl groups on N^x-CBZ-l -aspartic acid and N^α-CBZ-l -glutamic acid. Such selectivity is accomplished by initially protecting the a-carboxyl group through the formation of the corresponding 5-oxo-4-oxazolidinone ring. Following side-chain esterification, the α-carboxyl and α-amino groups are deprotected with acidolysis. Finally, the α-amino group is reprotected with the t-butyl-oxycarbonyl (Boc) group. Thus aspartic acid and glutamic acid have their side-chain carboxyl groups protected with the base-labile fluorenylmethyl ester (OFm) and their α-amino groups protected with the acid-labile Boc group. These residues, when used in conjunction with N^x-Boc-N^ε-Fmoc-l -lysine, are important in the formation of side-chain to side-chain cyclizations, via an amide bridge, during solid-phase peptide synthesis.     

Design,synthesis, and biological activities of a potent and selective α-melanotropin antagonist

Based on structure-activity relationships of the potent α-MSH agonist, Ac-Nle⁴-Asp⁵-His⁶-d -Phe⁷-Arg⁸-Trp⁹-Lys¹⁰-NH₂, several analogs of the general formula Ac-Nle⁴-Asp⁵-Waa⁶-Xaa⁷-Yaa⁸-Zaa⁹-Lys¹⁰-NH₂ were synthesized and tested on frog and lizard skin bioassays for their possible inhibitory actions against α-MSH on melanocyte stimulation. When Waa⁶= Trp, Xaa⁷= D-Phe, Yaa⁸= Nle and Zaa = Trp, a highly potent α-MSH antagonist, Ac-Nle-Asp-Trp-d -Phe-Nle-Trp-Lys-NH., with selectivity on the frog skin α-MSH receptor system (PA₂= 8.4) was obtained. However, several modifications in the amino acid sequence of the peptide resulted in a complete loss of antagonistic activity and a recovery of very weak agonistic action. The following changes in the amino acid sequence of the peptide were examined; His or d -Trp for Waa, l -Phe for Xaa, Arg, Ala or Pro for Yaa, and d -TV for Zaa. All resulted in full agonists with no antagonistic activity. In addition, lactam cyclization between the Asp⁵ and Lys¹⁰ side chains in the antagonist gave a full agonist and a complete loss of antagonistic activity. Efforts to develop a rational approach for the design of selective α-MSH antagonists for the frog skin α-MSH receptor will be discussed.