Protein surface recognition by synthetic receptors: A route to novel submicromolar inhibitors for α-chymotrypsin

Hyung Soon Park, Qing Lin, Andrew D. Hamilton

Research output: Contribution to journalArticle

Abstract

A family of synthetic receptors for protein surface recognition has been prepared. The receptors are based on a design in which four peptide loops are arrayed around a central calilx[4]arene core. By varying the sequence of the loop regions a range of differently functionalized receptor surfaces approximately 450 Å2 in area can be prepared. From this family we have identified potent inhibitors of chymotrypsin that function by binding to the surface of the protein. The most potent of these (1) shows slow binding kinetics in an analogous manner to several of the natural protein proteinase inhibitors. Detailed kinetic analysis showed 1 to be a competitive inhibitor with K(i) and K(i)* values of 0.81 and 0.11 μM, respectively.

Original languageEnglish (US)
Pages (from-to)8-13
Number of pages6
JournalJournal of the American Chemical Society
Volume121
Issue number1
DOIs
StatePublished - Jan 13 1999

Fingerprint

Artificial Receptors
Chymotrypsin
Membrane Proteins
Proteins
Kinetics
Peptide Hydrolases
Peptides

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Protein surface recognition by synthetic receptors : A route to novel submicromolar inhibitors for α-chymotrypsin. / Park, Hyung Soon; Lin, Qing; Hamilton, Andrew D.

In: Journal of the American Chemical Society, Vol. 121, No. 1, 13.01.1999, p. 8-13.

Research output: Contribution to journalArticle

@article{bf7b941093b749daba80b98d06e102dc,
title = "Protein surface recognition by synthetic receptors: A route to novel submicromolar inhibitors for α-chymotrypsin",
abstract = "A family of synthetic receptors for protein surface recognition has been prepared. The receptors are based on a design in which four peptide loops are arrayed around a central calilx[4]arene core. By varying the sequence of the loop regions a range of differently functionalized receptor surfaces approximately 450 {\AA}2 in area can be prepared. From this family we have identified potent inhibitors of chymotrypsin that function by binding to the surface of the protein. The most potent of these (1) shows slow binding kinetics in an analogous manner to several of the natural protein proteinase inhibitors. Detailed kinetic analysis showed 1 to be a competitive inhibitor with K(i) and K(i)* values of 0.81 and 0.11 μM, respectively.",
author = "Park, {Hyung Soon} and Qing Lin and Hamilton, {Andrew D.}",
year = "1999",
month = "1",
day = "13",
doi = "10.1021/ja981504o",
language = "English (US)",
volume = "121",
pages = "8--13",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "1",

}

TY - JOUR

T1 - Protein surface recognition by synthetic receptors

T2 - A route to novel submicromolar inhibitors for α-chymotrypsin

AU - Park, Hyung Soon

AU - Lin, Qing

AU - Hamilton, Andrew D.

PY - 1999/1/13

Y1 - 1999/1/13

N2 - A family of synthetic receptors for protein surface recognition has been prepared. The receptors are based on a design in which four peptide loops are arrayed around a central calilx[4]arene core. By varying the sequence of the loop regions a range of differently functionalized receptor surfaces approximately 450 Å2 in area can be prepared. From this family we have identified potent inhibitors of chymotrypsin that function by binding to the surface of the protein. The most potent of these (1) shows slow binding kinetics in an analogous manner to several of the natural protein proteinase inhibitors. Detailed kinetic analysis showed 1 to be a competitive inhibitor with K(i) and K(i)* values of 0.81 and 0.11 μM, respectively.

AB - A family of synthetic receptors for protein surface recognition has been prepared. The receptors are based on a design in which four peptide loops are arrayed around a central calilx[4]arene core. By varying the sequence of the loop regions a range of differently functionalized receptor surfaces approximately 450 Å2 in area can be prepared. From this family we have identified potent inhibitors of chymotrypsin that function by binding to the surface of the protein. The most potent of these (1) shows slow binding kinetics in an analogous manner to several of the natural protein proteinase inhibitors. Detailed kinetic analysis showed 1 to be a competitive inhibitor with K(i) and K(i)* values of 0.81 and 0.11 μM, respectively.

UR - http://www.scopus.com/inward/record.url?scp=0003042169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0003042169&partnerID=8YFLogxK

U2 - 10.1021/ja981504o

DO - 10.1021/ja981504o

M3 - Article

AN - SCOPUS:0003042169

VL - 121

SP - 8

EP - 13

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 1

ER -