TY - JOUR
T1 - A Convergent Solid-Phase Synthesis of Actinomycin Analogues - Towards Implementation of Double-Combinatorial Chemistry
AU - Tong, Glenn
AU - Nielsen, John
PY - 1996
Y1 - 1996
N2 - The actinomycin antibiotics bind to nucleic acids via both intercalation and hydrogen bonding. We found this 'double-action attack' mechanism very attractive in our search for a novel class of nucleic acid binders. A highly convergent, solid-phase synthetic strategy has been developed for a class of peptide-aryl-peptide conjugates modeled upon natural actinomycins. The features of this method include the use of Fmoc solid-phase peptide synthesis, side-chain to side-chain cyclization on the solid phase, a chemoselective cleavage step and segment condensation. The synthetic scheme is consistent with the requirements for combinatorial synthesis and furthermore, the final segment condensation allows, for the first time, double-combinatorial chemistry to be performed where two combinatorial libraries can be reacted with each other. Copyright (C) 1996 Elsevier Science Ltd.
AB - The actinomycin antibiotics bind to nucleic acids via both intercalation and hydrogen bonding. We found this 'double-action attack' mechanism very attractive in our search for a novel class of nucleic acid binders. A highly convergent, solid-phase synthetic strategy has been developed for a class of peptide-aryl-peptide conjugates modeled upon natural actinomycins. The features of this method include the use of Fmoc solid-phase peptide synthesis, side-chain to side-chain cyclization on the solid phase, a chemoselective cleavage step and segment condensation. The synthetic scheme is consistent with the requirements for combinatorial synthesis and furthermore, the final segment condensation allows, for the first time, double-combinatorial chemistry to be performed where two combinatorial libraries can be reacted with each other. Copyright (C) 1996 Elsevier Science Ltd.
U2 - 10.1016/0968-0896(96)00065-X
DO - 10.1016/0968-0896(96)00065-X
M3 - Journal article
SN - 0968-0896
VL - 4
SP - 693
EP - 698
JO - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
IS - 5
ER -