TY - JOUR
T1 - An α-helical peptidomimetic inhibitor of the HIV-1 Rev-RRE interaction
AU - Mills, Nicholas L.
AU - Daugherty, Matthew D.
AU - Frankel, Alan D.
AU - Guy, R. Kiplin
PY - 2006/3/22
Y1 - 2006/3/22
N2 - The interaction between the HIV-1 Rev protein and the Rev-Responsive Element (RRE) RNA is an attractive target for anti-viral therapy. We have designed α-helical peptidomimetics of Rev-like peptides using side chain-side chain macrolactam formation between positions i and i+4. One peptidomimetic having an appropriate location, orientation, and length of the macrolactam exhibited both significant helical character and specific RRE binding. This molecule displays 2-fold greater RNA specificity than the wild-type Rev peptide and more than 20-fold greater specificity than an uncyclized control peptide. Thus, specific, high affinity recognition of the RRE is feasible utilizing a small, relatively rigid peptidomimetic scaffold.
AB - The interaction between the HIV-1 Rev protein and the Rev-Responsive Element (RRE) RNA is an attractive target for anti-viral therapy. We have designed α-helical peptidomimetics of Rev-like peptides using side chain-side chain macrolactam formation between positions i and i+4. One peptidomimetic having an appropriate location, orientation, and length of the macrolactam exhibited both significant helical character and specific RRE binding. This molecule displays 2-fold greater RNA specificity than the wild-type Rev peptide and more than 20-fold greater specificity than an uncyclized control peptide. Thus, specific, high affinity recognition of the RRE is feasible utilizing a small, relatively rigid peptidomimetic scaffold.
UR - http://www.scopus.com/inward/record.url?scp=33645390844&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645390844&partnerID=8YFLogxK
U2 - 10.1021/ja0582051
DO - 10.1021/ja0582051
M3 - Article
C2 - 16536504
AN - SCOPUS:33645390844
SN - 0002-7863
VL - 128
SP - 3496
EP - 3497
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 11
ER -