ISSN:1075-2617    

DOI:10.1002/psc.2763

年代:2015

数据来源: WILEY

摘要:

Geoffrey Tyndale Young was born in England's Peak District in 1915: his father and both grandfathers were pharmaceutical chemists. He graduated from the Universities of Birmingham and Bristol and was a transatlantic scientific liaison officer in the Second World War, shortly after which he was elected to a Fellowship at Jesus College Oxford. He combined peptide synthesis research, undergraduate teaching, and College administration with leadership in European peptide science and was universally respected for his integrity, wisdom, and unflappable diplomacy. A close friend of Josef Rudinger, he attended almost all of the first two dozen European Peptide Symposia 1958–1996. When he retired in 1982, he was appointed an Officer of the Order of the British Empire and was elected an Emeritus Fellow of Jesus College, of which he had been Acting Principal 1973–1977. In retirement, he was instrumental in setting up this journal and steered the formation of the European Peptide Society, of which he was the first chairman. In 1950, he married Janet Mary Baker, later Baroness Young of Farnworth, Leader of the British House of Lords 1982–1983, who died in 2002: they had three daughters who survive him. He died at home in Oxford on 24 May 2014 aged 98. Copyright © 2014 European Peptide Society and John Wiley&Son

ISSN:1075-2617    

DOI:10.1002/psc.2720

年代:2015

数据来源: WILEY

摘要:

Peptide chemistry plays a key role in the synthesis and study of protein molecules and their functions. Modern ligation methods enable the total synthesis of enzymes and the systematic dissection of the chemical basis of enzyme catalysis. Predicted developments in peptide science are described. Copyright © 2015 European Peptide Society and John Wiley&Sons, Ltd

ISSN:1075-2617    

DOI:10.1002/psc.2754

年代:2015

数据来源: WILEY

摘要:

Intramolecular acyl transfer equilibrium in peptides and proteins has stimulated the development of new methodologies for ligation, aggregation suppression or difficult peptide synthesis. Native chemical ligation or aggregation suppression methodologies are based on an X‐to‐N acyl transfer of a peptide chain (X = S, O). The reverse reaction from N‐to‐X has led to exciting developments in solving key synthetic problems such as peptide thioester preparation using Fmoc/tBu strategy. Depending on the target peptide or protein, variations of these methods, which are also based on acyl transfer equilibriums, are now available.In this review, we provide a detailed overview of development and utility of methodologies in peptide chemistry that are based on the control of intramolecular equilibrium. To this end, we outline the scaffolds that are favorable for acyl transfer, the conditions for controlling both sides of the acyl transfer equilibrium and their applications to peptide and protein chemistry. Additional new methodologies have been developed for the synthesis of difficult peptides such as peptide alcohols or head‐to‐tail cyclic peptides. Promising new applications of intramolecular acyl transfer reactions are also highlighted. Copyright © 2015 European Peptide Society and John

ISSN:1075-2617    

DOI:10.1002/psc.2749

年代:2015

数据来源: WILEY

摘要:

In this second part of our review article on the preferred screw sense and interconversion of peptide helices, we discuss the most significant computational and experimental data published on helices formed by the most extensively investigated categories of noncodedα‐amino acids. They are as follows: (i)N‐alkylated Gly residues (peptoids), (ii) Cα‐alkylatedα‐amino acids, (iii) Cα,β‐sp2configuratedα‐amino acids, and (iv) combinations of residues of types (ii) and (iii). With confidence, the large body of interesting papers examined and classified in this editorial effort will stimulate the development of helical peptides in many diverse areas of biosciences and nanosciences. Copyright © 2015 European Peptide Society and Jo

ISSN:1075-2617    

DOI:10.1002/psc.2743

年代:2015

数据来源: WILEY

摘要:

Despite the intensive study on the mechanism of action of membrane‐active molecules such as antimicrobial and anticancer peptides, most of the biophysical work has been performed using artificial model systems, mainly lipid vesicles. The use of these systems allows full control of the experimental parameters, and to obtain molecular‐level detail on the action of peptides, the correlation with biological action is intangible. Recently, several biophysical methodologies have been translated to studies using bacterial and cancer cells. Here, we review biophysical studies on the mechanism of action of antimicrobial and anticancer peptides performed directly on cells. The data in these studies allow to correlate vesicle‐based and cell‐based studies and fill the vesicle‐cell interdisciplinary gap. Copyright © 2015 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.2741

年代:2015

数据来源: WILEY

摘要:

Most toxic agents currently used for chemotherapy show a narrow therapeutic window, because of their inability to distinguish between healthy and cancer cells. Targeted drug delivery offers the possibility to overcome this issue by selectively addressing structures on the surface of cancer cells, therefore reducing undesired side effects. In this broad field, peptide–drug conjugates linked by intracellular cleavable structures have evolved as highly promising agents. They can specifically deliver toxophores to tumor cells by targeting distinct receptors overexpressed in cancer. In this review, we focus on these compounds and describe important factors to develop a highly efficient peptide–drug conjugate. The necessary properties of tumor‐targeting peptides are described, and the different options for cleavable linkers used to connect toxic agents and peptides are discussed, and synthetic considerations for the introduction of these structures are reported. Furthermore, recent examples and current developments of peptide–drug conjugates are critically evaluated with a special focus on the applied linker structures and their future use in cancer therapy. Copyright © 2015 European Peptide Society and John Wiley&S

ISSN:1075-2617    

DOI:10.1002/psc.2753

年代:2015

数据来源: WILEY

摘要:

Peptide hydrazides are valuable building blocks in peptide and protein chemistry, e.g. as precursors of peptide thioesters that allow the preparation of these important intermediates under mild conditions. Additional robust and versatile methods for the generation of peptide hydrazides from standard solid supports are therefore highly desired in order to facilitate access to peptide thioester via Fmoc‐based SPPS.Here, the efficient generation of peptide hydrazides from conventional 4‐hydroxymethyl phenol Wang‐TentalGel peptidyl resins is described. Direct hydrazinolysis of a 19mer mucin1 peptide gives the protected peptide hydrazide in excellent yields. Testing a series of octapeptides carrying the 20 common proteinogenic amino acids at their C‐terminus led to preparation of all corresponding peptide hydrazides in very good to excellent yields and purities. The available set of octapeptides allowed analyzing the influence of the nature of the C‐terminal amino acid and of the solvent on the hydrazinolysis reaction. Furthermore, the compatibility of the method with posttranslational modifications (here glycosylation) and with potentially sensitive functional groups in amino acid side chains makes this approach a viable alternative for obtaining peptide hydrazides. It combines the advantages of a straightforward synthesis with stereochemical stability and flexibility, as it provides easy access to the peptide acid and the peptide thioester (via the hydrazide) from the same solid support. Copyright © 2015 European Peptide Society and John Wiley

ISSN:1075-2617    

DOI:10.1002/psc.2747

年代:2015

数据来源: WILEY

摘要:

The crystal structure of a (4S)‐configured ammoniumproline derivative is presented. The trifluoroacetic acid salt of the acetylated methylester of (4S)‐aminoproline (Ac‐(4S)Amp‐OMe) crystallized as thetransconformer with a C(4)‐endoring pucker. The high‐resolution structure shows typical parameters for a transannular H‐bond and an n → π* interaction between the adjacent amide and ester groups. The structure corroborates previous findings of solution phase studies on the importance of these two interactions in acidic and neutral aqueous environments for the conformation of this pH‐responsive proline derivative. Copyright © 2015 European Peptide Society a

ISSN:1075-2617    

DOI:10.1002/psc.2734

年代:2015

数据来源: WILEY

摘要:

This report summarizes recent biophysical and protein expression experiments on polypeptides containing theN‐terminus, the first, second, and third transmembrane (TM) domains and the contiguous loops of the α‐factor receptor Ste2p, a G protein‐coupled receptor. The 131‐residue polypeptide Ste2p(G31‐R161), TM1–TM3, was investigated by solution NMR in trifluoroethanol/water. TM1–TM3 contains helical TM domains at the predicted locations, supported by continuous sets of medium‐range NOEs. In addition, a short helixN‐terminal to TM1 was detected, as well as a short helical stretch in the first extracellular loop. Two 161‐residue polypeptides, [Ste2p(M1‐R161), NT–TM1–TM3],that contain the entireN‐terminal sequence, one with a single mutation, were directly expressed and isolated fromEscherichia coliin yields as high as 30 mg/L. Based on its increased stability, the L11P mutant will be used in future experiments to determine long‐range interactions. The study demonstrated that 3‐TM domains of a yeast G protein‐coupled receptor can be produced in isotopically labeled form suitable for solution NMR studies. The quality of spectra is superior to data recorded in micelles and allows more rapid data analysis. No tertiary contacts have been determined, and if present, they are likely transient. This observation supports earlier studies by us that secondary structure was retained in smaller fragments, both in organic solvents and in detergent micelles, but that stable tertiary contacts may only be present when the protein is imbedded in lipids. Copyright © 2015 European Pep

ISSN:1075-2617    

DOI:10.1002/psc.2750

年代:2015

数据来源: WILEY