摘要:

AbstractDuring the past decade proteases have been widely used as catalysts in peptide synthesis. Unfortunately, they are not ideal ligases. Enzymatic peptide synthesis in frozen aqueous systems has been developed as an approach towards the suppression of competitive reactions. This paper summarizes reports concerning the behaviour of non‐enzymatic as well as of enzyme‐catalysed reactions when the reaction mixture is frozen. The advantages of freezing the reaction mixture in serine and cysteine protease‐catalysed peptide synthesis, the influence of modified reaction conditions and the possible reasons for the yield‐increasing effect of freezing are di

ISSN:1075-2617    

DOI:10.1002/psc.65

出版商:John Wiley&Sons, Ltd.    

年代:1996

数据来源: WILEY

摘要:

AbstractThe sequence of deltorphin I, a δ‐selective opioid agonist, has been systematically modified by inserting conformationally constrained Cα,αdisubstituted apolar residues in the third position. As expected, substitution of Phe with Ac6c, Ac5c and Ac3c yields analogues with decreasing but sizeable affinity. Surprisingly, substitution with Aib yields an analogue with almost the same binding affinity of the parent compound but with a greatly increased selectivity. This is the first case of a potent and very selective opioid peptide containing a single aromatic residue in the message domain, that is, only Tyr1. Here we report a detailed conformational analysis of [Aib3]deltorphin I and [Ac6c3]deltorphin I in DMSO at room temperature and in a DMSO/water cryomixture at low temperature, based on NMR spectroscopy and energy calculations. The peptides are highly structured in both solvents, as indicated by the exceptional finding of a nearly zero temperature coefficient of Val5NH resonance. NMR data cannot be explained on the basis of a single structure but it was possible to interpret all NMR data on the basis of a few structural families. The conformational averaging was analysed by means of an original computer program that yields qualitative and quantitative composition of the mixture. Comparison of the preferred solution conformations with two rigid δ‐selective agonists shows that the shapes of [Aib3]deltorphin I and [Ac6c3]deltorphin I are consistent with those of rigid agonists and that the message domain of opioid peptides can be defined only in conformationa

ISSN:1075-2617    

DOI:10.1002/psc.56

出版商:John Wiley&Sons, Ltd.    

年代:1996

数据来源: WILEY

摘要:

Abstractω‐Agatoxin IVA, isolated from the venom of funnel web spiderAgelenopsis aperta,blocks potently and selectively P‐type calcium channels. This toxin, composed of 48 amino acids and containing 8 cysteine residues, was synthesized by the solid‐phase procedure. The Cys residues were protected by acetamidomethyl (Acm) groups which were removed by mercuric acetate. During treatment with mercuric acetate, a by‐product was detected, involving modification of tryptophan residues by the Acm groups. This side reaction can be completely prevented by addition of an excess of tryptophan in the reaction medium during Acm deprotection.The resulting peptide was submitted to an oxidative refolding, in different conditions, in order to determine the most favourable protocol. After formation of the four disulphide bonds, the toxin was purified by successive preparative HPLC, on two different supports, and fully characterized by analytical HPLC, capillary electrophoresis, amino acid analysis, mass spectrometry and Edman degradation. It was found to block the P‐type calcium channel with a similar biological potency as described for the natur

ISSN:1075-2617    

DOI:10.1002/psc.57

出版商:John Wiley&Sons, Ltd.    

年代:1996

数据来源: WILEY

摘要:

AbstractTaking into account the sequence homology existing between thymopoietin II and the DNA‐binding domain of p53 protein, a series of octapeptides was synthesized, related to the wild p53 type protein as well as to its mutated forms, appearing in some human tumours. The wild type octapeptide has immunostimulative activity with regard to the humoral immune response, but is inactive in the cellular immune response. The mutated peptides of p53 differ in their immunomodulatory activity from the wild type octapeptide. The Ser5 analogue of the wild type peptide is a strong stimulant of the humoral immune response and enhances TNF‐α production, while at the same time suppressing the cellular immune response. The data suggest that the mutations of p53, which favour tumour development and growth, may also change the immune activity of respective p53 fragm

ISSN:1075-2617    

DOI:10.1002/psc.68

出版商:John Wiley&Sons, Ltd.    

年代:1996

数据来源: WILEY

摘要:

AbstractWe synthesized by classical solution methods three conformational constrained analogues of EDNEYTA, a heptapeptide sequence that represents the common major autophosphorylation site of the protein tyrosine kinases (PTKs) of the Src family. The correlation between the different structural properties induced by the modifications of the native sequence and the propensity of the peptides to act as PTK substrates was examined. The kinetic data obtained indicate that the introduction of the tyrosine‐analogue constraints Tic(OH) and MeTyr, which block the ring flexibility, completely prevents the phosphorylation catalysed by the kinases Lyn and Fgr. On the other hand PTKIIB/p38sykcan phosphorylate the two derivatives albeit with an efficiency lower than that found with the native sequence. A third derivative contained side chain to side chain cyclization. This analogue, in which the freedom of the phenolic moiety is not altered, can be phosphorylated by all the PTKs tested with kinetic constants comparable to the parent peptid

ISSN:1075-2617    

DOI:10.1002/psc.70

出版商:John Wiley&Sons, Ltd.    

年代:1996

数据来源: WILEY

ISSN:1075-2617    

DOI:10.1002/psc.310020501

出版商:John Wiley&Sons, Ltd.    

年代:1996

数据来源: WILEY