Publication Date:
1992-04-10
Description:
Backbone-engineered HIV-1 protease was prepared by a total chemical synthesis approach that combines the act of joining two peptides with the generation of an analog structure. Unprotected synthetic peptide segments corresponding to the two halves of the HIV-1 protease monomer polypeptide chain were joined cleanly and in high yield through unique mutually reactive functional groups, one on each segment. Ligation was performed in 6 molar guanidine hydrochloride, thus circumventing limited solubility of protected peptide segments, the principal problem of the classical approach to the chemical synthesis of proteins. The resulting fully active HIV-1 protease analog contained a thioester replacement for the natural peptide bond between Gly51-Gly52 in each of the two active site flaps, a region known to be highly sensitive to mutational changes of amino acid side chains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schnolzer, M -- Kent, S B -- New York, N.Y. -- Science. 1992 Apr 10;256(5054):221-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1566069" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Guanidine
;
Guanidines
;
HIV Protease/*chemical synthesis/metabolism
;
HIV-1/*enzymology
;
Indicators and Reagents
;
Mass Spectrometry
;
Models, Molecular
;
Molecular Sequence Data
;
Peptides/*chemical synthesis
;
Protein Conformation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
