Biomedical subjects

A S Weichsel

Publications and source records attributed to A S Weichsel.

3 recordsLinked to original sources

PubMed1996

Structurally homogeneous and heterogeneous synthetic combinatorial libraries.

We have designed and synthesized structurally homogeneous and heterogeneous nonpeptide libraries. Structurally homogeneous libraries are characterized by the presence of one common structural unit, a scaffold, in all library compounds (e.g. cyclopentane, cyclohexane, diketopiperazine, thiazolidine). In structurally heterogeneous libraries different organic reactions (acylation, etherification, reductive amination, nucleophilic displacement) were applied to connect bifunctional building blocks unrelated in structure (aromatic hydroxy acids, aromatic hydroxy aldehydes, amino alcohols, diamines, and amino acids). The focus of this communication is to document the use of bifunctional building blocks for the design and synthesis of structurally heterogeneous libraries of N-(alkoxy acyl)amino acids, N,N'-bis-(alkoxy acyl)diamino acids, N-acylamino ethers, N-(alkoxy acyl)amino alcohols, N-alkylamino ethers, and N-(alkoxy aryl)diamines.

Aldehydes↗

PubMed1996

Bifunctional scaffolds as templates for synthetic combinatorial libraries.

A small-molecule synthetic combinatorial library was designed and synthesized that features potential pharmacophores attached to a variety of small cyclic scaffolds. The synthesis of the library involved randomization of three types of building blocks: 20 amino acids, 10 aromatic hydroxy acids and 21 alcohols, totaling a library complexity of 4200 compounds. Mitsunobu polymer-supported etherification was used in the last randomization. The library compounds were attached to beads via an ester-bond linkage enabling both on-bead as well as in-solution screening. When the library was tested against a model target, streptavidin, specific binders were found. The structures of the most active compounds were determined from the fragmentation pattern in MS/MS experiments.

Alcohols↗

PubMedDate not supplied

Linear presentation of variable side-chain spacing in a highly diverse combinatorial library.

A synthetic library that presents potential pharmacophores in a linear fashion with variable spacing was designed (alpha, beta, gamma-library). To prove the concept, we synthesized a number of individual compounds as well as a model library. Diamino acids connected by amide bonds via their alpha- or side-chain amino groups were used to form the backbone (scaffold) of this library. The remaining amino group of the diamino acids were acylated by a variety of carboxylic acids, generating an appreciable diversity of compounds in this library. The compositions of compounds in the library were identified by reading a peptide tag synthesized concurrently with the library structures. This code contained the information regarding the carboxylic acid coupled, and the diamino acid and amino group to which the acid was coupled.

Amino Acid Sequence↗