開發以D-型胺基酸置換與PEG接合增長胜?藥在體內循環時間的方法;Circulation Time Extension of Peptide Drugs by D-Scanning and Pegylation

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Title:	開發以D-型胺基酸置換與PEG接合增長胜?藥在體內循環時間的方法;Circulation Time Extension of Peptide Drugs by D-Scanning and Pegylation
Authors:	阮若屈
Contributors:	國立中央大學化學工程與材料工程學系
Keywords:	化學工程;生物技術(醫)
Date:	2012-12-01
Issue Date:	2014-03-17 11:30:06 (UTC+8)
Publisher:	行政院國家科學委員會
Abstract:	研究期間：10108~10207;Indolicidin (IL) is a cationic antimicrobial peptide which contains thirteen amino acid residues. It has a wide antimicrobial spectrum such as Gram-positive and Gram-negative bacteria, fungi, and it can even inhibit the attack from HIV、HSV-1and HSV-2 virus. Through the help of molecular dynamic simulation we have designed an indolicidin analogue to own much higher bactericidity and much lower hemolytic activity. But there is still one problem need to be resolved: How to avoid peptide degradation by proteases? We propose two methods to resolve this problem: one is D-amino acid substitution, the other is peptide PEGylation. The disadvantages of D-amino acid substitution are cost increasing and possible activity alteration. We, therefore, try to reduce the number of D-amino acid substitution and study the possible alteration of peptide’s bio-activity. The disadvantage of peptide PEGylation is activity reduction. Therefore, we try to insert a MMP-1 cutting site between the antimicrobial peptide and PEG. We expect that the high concentration of MMP near inflammatory region will cut off the PEG segment. The difficulties are how to select the length of PEG in order to protect peptides against protease attack, but at the same time allow MMP cleavage. The success of this project can help the peptide drug design for effective drug delivery.
Relation:	財團法人國家實驗研究院科技政策研究與資訊中心
Appears in Collections:	[Department of Chemical and Materials Engineering] Research Project

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