Topic
Bicyclic molecule
About: Bicyclic molecule is a research topic. Over the lifetime, 29587 publications have been published within this topic receiving 451252 citations. The topic is also known as: bicyclic molecule.
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TL;DR: A phage strategy for the selection of ligands based on bicyclic or linear peptides attached covalently to an organic core for generating and selecting bicyclic macrocycles as ligands poised at the interface of small-molecule drugs and biologics is described.
Abstract: Here we describe a phage strategy for the selection of ligands based on bicyclic or linear peptides attached covalently to an organic core. We designed peptide repertoires with three reactive cysteine residues, each spaced apart by several random amino acid residues, and we fused the repertoires to the phage gene-3-protein. Conjugation with tris-(bromomethyl)benzene via the reactive cysteines generated repertoires of peptide conjugates with two peptide loops anchored to a mesitylene core. Iterative affinity selections yielded several enzyme inhibitors; after further mutagenesis and selection, we were able to chemically synthesize a lead inhibitor (PK15; Ki = 1.5 nM) specific to human plasma kallikrein that efficiently interrupted the intrinsic coagulation pathway in human plasma tested ex vivo. This approach offers a powerful means of generating and selecting bicyclic macrocycles (or if cleaved, linear derivatives thereof) as ligands poised at the interface of small-molecule drugs and biologics.
576 citations
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572 citations
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06 May 1992TL;DR: In this article, a method of inhibiting abnormal cell proliferation in a patient suffering from a disorder characterized by such proliferation comprising the administration of an EGF and/or PDGF receptor inhibiting effective amount of said bis mono-and/or bicyclic aryl/or heteroaryl compound and their preparation of said compounds and their use in pharmaceutical compositions used in this method.
Abstract: This invention relates to bis mono- and/or bicyclic aryl and/or heteroaryl compounds exhibiting protein tyrosine kinase inhibition activity. More specifically, it relates to the method of inhibiting abnormal cell proliferation in a patient suffering from a disorder characterized by such proliferation comprising the administration thereto of an EGF and/or PDGF receptor inhibiting effective amount of said bis mono- and/or bicyclic aryl and/or heteroaryl compound and to the preparation of said compounds and their use in pharmaceutical compositions used in this method.
546 citations
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533 citations
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06 Jun 1995TL;DR: In this paper, the formulae I and Ia and their racemates, in which A is a purine or pyrimidine radical or an analogue thereof, can be used as antiviral active ingredients or for the preparation of biologically active oligonucleotides.
Abstract: Compounds of the formulae I and Ia and their racemates ##STR1## in which A is --CH 2 -- or --CH 2 CH 2 --, R 1 is hydrogen or a protective group, R 2 is hydrogen or a protective group or a radical forming a phosphorus-containing nucleotide bridge group and B is a purine or pyrimidine radical or an analogue thereof, can be used as antiviral active ingredients or for the preparation of biologically active oligonucleotides.
531 citations