co9b00199_si_001.pdf (12.11 MB)
Homogeneous and Functional Group Tolerant Ring-Closing Metathesis for DNA-Encoded Chemical Libraries
journal contribution
posted on 2020-01-17, 22:29 authored by Olivier B. C. Monty, Pranavanand Nyshadham, Kurt M. Bohren, Murugesan Palaniappan, Martin M. Matzuk, Damian W. Young, Nicholas SimmonsReaction
heterogeneity, poor pH control, and catalyst decomposition in the
ring-closing metathesis (RCM) of DNA–chemical conjugates lead
to poor yields of the cyclized products. Herein we address these issues
with a RCM reaction system that includes a novel aqueous solvent combination
to enable reaction homogeneity, an acidic buffer system which masks
traditionally problematic functional groups, and a decomposition-resistant
catalyst which maximizes conversion to the cyclized product. Additionally,
we provide a systematic study of the substrate scope of the on-DNA
RCM reaction, a demonstration of its applicability to a single-substrate
DNA-encoded chemical library that includes sequencing analysis, and
the first successful stapling of an unprotected on-DNA [i, i+4] peptide.
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DNA-Encoded Chemical Libraries Reaction heterogeneityring-closing metathesiscyclized productsubstrate scopesequencing analysison-DNA RCM reactionreaction homogeneityFunctional Group Tolerant Ring-Closing Metathesissingle-substrate DNA-encoded chemical librarypH controlcyclized productsacidic buffer systemRCM reaction systemdecomposition-resistant catalystcatalyst decomposition
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