摘要:

AbstractA new and cost‐effective linker for the generation of carboxylic acid end groups on Multipin supports (SynPhase™ crowns) has been developed. Synthesis of the linker was based on modification of grafted polystyrene (PS) crowns to generate a hydroxyethyl moiety which is acid labile in 10–20% trifluoroacetic acid (TFA) in dichloromethane (DCM). Solid‐phase syntheses of model decapeptides using this linker are described. Copyright © 2000 European Peptide Society and John Wiley&S

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200002)6:2<49::AID-PSC239>3.0.CO;2-6

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractThe biologically relevant conformation of substance P is likely to be dictated by the lipid milieu wherein the hormone would interact with its receptor. Assuming that specific constraints to the hormone structure may be imparted by its interaction with Ca2+ions in the low dielectric lipid medium, the interaction of substance P and its inactive analog, Ala7‐substance P, has been characterized in a lipid‐mimetic solvent. Circular dichroism (CD) and NMR spectral methods were employed to study the conformation of the free and Ca2+‐bound forms of the peptides and the conformational changes that occur on Ca2+binding. The results show that both peptides assume a helical structure in the non‐polar solvent used, a mixture of acetonitrile and trifluoroethanol. TheN‐terminal region is, however, less ordered in the analog peptide compared with the native hormone. Ca2+addition causes significant conformational changes in both the peptides. However, while substance P binds two Ca2+ions in a cooperative manner, Ala7‐substance P binds only one Ca2+ion with a relatively weaker affinity. Computations of the minimum‐energy conformations of the free and Ca2‐bound peptides were performed usinginterproton distances derived from nuclear Overhauser enhancement spectra of the two peptides, as well as the information provided by changes in proton chemical shifts caused by Ca2+addition. Taken together, the results of this study suggest that differences in the interaction of substance P and Ala7‐substance P with Ca2+in the non‐polar milieu, which in turn leads to differences in their Ca2+‐bound conformations, may be the basis for the differences in their biological potencies. Copyright © 2000 European Peptide Society an

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200002)6:2<57::AID-PSC245>3.0.CO;2-M

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY

摘要:

AbstractIn the synthesis of large peptides or proteins, highly homogeneous segments are indispensable for a convergent strategy either on a solid‐phase resin or in solution. Employing Boc/Bzl chemistry to prepare fully protected segments with a free α‐carboxyl group from the solid support, base‐labile linkers are profitable for practical peptide synthesis since they require no special equipment. For this purpose, anN‐[9‐(hydroxymethyl)‐2‐fluorenyl]succinamic acid (HMFS) linker was adopted. Consequently, there must be high compatibility between the protecting groups of the segment and the anchoring group which is cleavable by treatment with morpholine or piperidine in DMF. Instead of using the 2‐bromobenzyloxycarbonyl (BrZ) group for the Tyr residue and the formyl (For) group for the Trp residue, both of which are the most susceptible protecting groups under these base‐catalysed conditions, the base‐resistant 3‐pentyl (Pen) and cyclohexyloxycarbonyl (Hoc) groups were introduced to the respective side‐chain functional groups. By applying the present strategy, the authors were able to rapidly synthesize homogeneous protected segments for use in the subsequent segment coupling in solution. In the present paper, the utility of the combined solid‐phase and solution approach is demonstrated by synthesizing muscarinic toxin 1 (MTX1) which binds to the muscarinic acetylcholine receptors. Copyright © 2000 European Peptide Socie

ISSN:1075-2617    

DOI:10.1002/(SICI)1099-1387(200002)6:2<84::AID-PSC246>3.0.CO;2-P

出版商:John Wiley&Sons, Ltd.    

年代:2000

数据来源: WILEY