Manipulation of unfolding-induced protein aggregation by peptides selected for aggregate-binding ability through phage display library screening.

Kundu, Bishwajit and Shukla, Anshuman and Guptasarma, Purnananda (2002) Manipulation of unfolding-induced protein aggregation by peptides selected for aggregate-binding ability through phage display library screening. Biochemical and biophysical research communications, 291 (4). pp. 903-7. ISSN 0006-291X

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Abstract

A phage-displayed library of peptides (12-mer) was screened for the ability to bind to thermally aggregated bovine carbonic anhydrase (BCA), with a view toward examining whether peptides possessing this ability might bind to partially structured intermediates on the protein's unfolding pathway and, therefore, constitute useful tools for manipulation of the kinetic partitioning of molecules between the unfolded and aggregated states. Two peptides [N-HPSTMGLRTMHP-C and N-TPSAWKTALVKA-C] were identified and tested. While neither showed thermal aggregation autonomously, both peptides individually elicited remarkable increases in the levels of thermal aggregation of BCA. A possible explanation is that both peptides bind to surfaces on molten BCA that are not directly involved in aggregation. Such binding could slow down interconversions between folded and unfolded states and stabilize aggregation-prone intermediate(s) to make them more prone to aggregation, while failing to achieve any steric prevention of aggregation. The approach has the potential of yielding useful aggregation-aiding/inhibiting agents, and may provide clues to whether amorphous aggregates are "immobilized" forms of folding intermediates.

Item Type:	Article
Additional Information:	Copyright of this article belongs to Elsevier Science.
Uncontrolled Keywords:	thermal unfolding; protein aggregation; phage display; folding intermediates
Subjects:	Q Science > QD Chemistry
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	05 Jan 2012 15:15
Last Modified:	05 Jan 2012 15:15
URI:	http://crdd.osdd.net/open/id/eprint/275

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