A convergent solid-phase synthesis of actinomycin analogues - towards implementation of double-combinatorial chemistry

TY - JOUR

T1 - A convergent solid-phase synthesis of actinomycin analogues - towards implementation of double-combinatorial chemistry

AU - Tong, Glenn

AU - Nielsen, John

PY - 1996/5/1

Y1 - 1996/5/1

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.

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.

U2 - 10.1016/0968-0896(96)00065-X

DO - 10.1016/0968-0896(96)00065-X

M3 - Journal article

C2 - 8804535

AN - SCOPUS:0029890756

SN - 0968-0896

VL - 4

SP - 693

EP - 698

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 5

ER -