A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries

Darwen, PJ, Tran, TT, Bourne, GT, Nielson, JL and Smythe, ML (2006) A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries. Combinatorial Chemistry & High Throughput Screening, 9 7: 559-563.


Author Darwen, PJ
Tran, TT
Bourne, GT
Nielson, JL
Smythe, ML
Title A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries
Journal name Combinatorial Chemistry & High Throughput Screening   Check publisher's open access policy
ISSN 1386-2073
Publication date 2006
Sub-type Article (original research)
DOI 10.2174/138620706777935333
Volume 9
Issue 7
Start page 559
End page 563
Total pages 5
Editor Richard. Van Breeman
Place of publication The Netherlands
Publisher Bentham Science Publishers Ltd
Collection year 2006
Language eng
Subject C1
250699 Theoretical and Computational Chemistry not elsewhere classified
780103 Chemical sciences
Abstract Combinatorial chemistry has become an invaluable tool in medicinal chemistry for the identification of new drug leads. For example, libraries of predetermined sequences and head-to-tail cyclized peptides are routinely synthesized in our laboratory using the IRORI approach. Such libraries are used as molecular toolkits that enable the development of pharmacophores that define activity and specificity at receptor targets. These libraries can be quite large and difficult to handle, due to physical and chemical constraints imposed by their size. Therefore, smaller sub-libraries are often targeted for synthesis. The number of coupling reactions required can be greatly reduced if the peptides having common amino acids are grouped into the same sub-library (batching). This paper describes a schedule optimizer to minimize the number of coupling reactions by rotating and aligning sequences while simultaneously batching. The gradient descent method thereby reduces the number of coupling reactions required for synthesizing cyclic peptide libraries. We show that the algorithm results in a 75% reduction in the number of coupling reactions for a typical cyclic peptide library.
Keyword Cyclic Peptides
Alignment
Batch Synthesis
Coupling Reaction
Gradient Descent
Hill Climbing
Combinatorial Chemistry
Split
Mix
Biochemical Research Methods
Chemistry, Applied
Pharmacology & Pharmacy
Drug Discovery
Privileged Structures
Molecular Diversity
Organic-synthesis
Generation
Technologies
Somatostatin
Cyclization
Strategies
Q-Index Code C1

 
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