摘要:

AbstractDendrimers are branched structures and represent a fast growing field covering many areas of chemistry. Various types of dendrimers differing in composition and structure are mentioned, together with their practical use spanning from catalysis, transport vehicles to synthetic vaccines. The main stress is given to peptide dendrimers, namely, multiple antigenic peptides (MAPs). Their synthesis, physicochemical properties, biological activities, etc. have been described with many examples. MAPs can be used as diagnostics, mimetics, for complexation of different cations, as vaccines against parasites, bacteria, viruses, etc. Copyright © 2005 European Peptide Society and John Wiley&Sons, Ltd

ISSN:1075-2617    

DOI:10.1002/psc.721

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractThe use of high‐throughput methods in drug discovery allows the generation and testing of a large number of compounds, but at the price of providing redundant information. Evolutionary combinatorial chemistry combines the selection and synthesis of biologically active compounds with artificial intelligence optimization methods, such as genetic algorithms (GA). Drug candidates for the treatment of central nervous system (CNS) disorders must overcome the blood–brain barrier (BBB). This paper reports a new genetic algorithm that searches for the optimal physicochemical properties for peptide transport across the blood–brain barrier. A first generation of peptides has been generated and synthesized. Due to the high content ofN‐methyl amino acids present in most of these peptides, their syntheses were especially challenging due to over‐incorporations, deletions and DKP formations. Distinct fragmentation patterns during peptide cleavage have been identified. The first generation of peptides has been studied by evaluation techniques such as immobilized artificial membrane chromatography (IAMC), a cell‐based assay, logPoctanol/watercalculations, etc. Finally, a second generation has been proposed. Copyright © 2005 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/psc.679

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractAs endocytic uptake of the Antennapedia homeodomain‐derived penetratin peptide (RQIKIWFQNRRMKWKK) is finally being revealed, some of the early views about penetratin need to be reconsidered. Endocytic uptake seems to contradict the indispensability of tryptophans and also the minimum length of 16 amino acid residues for efficient internalization. To revise the membrane translocation of penetratin, two penetratin analogs were designed and synthesized: a peptide in which tryptophans were replaced by phenylalanines (Phe6, 14‐penetratin,RQIKIFFQNRRMKFKK) and a shortened analog (dodeca‐penetratin,RQIKIWF‐R‐KWKK) made up of only 12 residues. The peptides were fluorescently labeled and applied to live, unfixed cells from various lines. Cellular uptake was analysed by confocal microscopy and flow cytometry. Low temperature or ATP‐depletion blocked the intracellular entry of all three penetratin peptides. A decrease in membrane fluidity or cholesterol depletion with methyl‐β‐cyclodextrin greatly inhibited peptide uptake, showing the involvement of cholesterol‐rich lipid rafts in internalization. Exogenous heparan sulfate also diminished the internalization of penetratin and its derivatives, reflecting the paramount importance of electrostatic interactions with polyanionic cell‐surface proteoglycans. The beneficial presence of tryptophans is supported by observations on the decreased cellular uptake of Phe6, 14‐penetratin. The maintained translocational efficiency of dodeca‐penetratin demonstrates that a thorough understanding of penetratin internalization can yield new penetratin analogs with unaltered translocational abilities.This study provides evidence on the energy‐dependent and lipid raft‐mediated endocytic uptake of penetratin and highlights the necessity of revealing those pathways that cationic cell‐penetrating peptides employ to enter live cells. Copyright © 2005 European Peptide S

ISSN:1075-2617    

DOI:10.1002/psc.678

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY

摘要:

AbstractA synthetic route to novel chiral PNA monomer‐cyclen conjugates was described for the first time, the targeted products were obtained in high yields under mild reaction conditions. The preliminary results demonstrated that the uracil‐PNA monomer‐cyclen conjugates can rapidly bind Zn2+in aqueous solution, and the structure of the Zn(II) complex was confirmed facilely by HRMS spectra,1H NMR spectra and elemental analysis. Copyright © 2005 European Peptide Society and John Wiley&Son

ISSN:1075-2617    

DOI:10.1002/psc.685

出版商:John Wiley&Sons, Ltd.    

年代:2005

数据来源: WILEY