Reflections on a Copenhagen-Minneapolis Axis in Bioorganic Chemistry

George Barany; Paul R Hansen

doi:10.3390/molecules29061317

Reflections on a Copenhagen-Minneapolis Axis in Bioorganic Chemistry

Molecules. 2024 Mar 15;29(6):1317. doi: 10.3390/molecules29061317.

Authors

George Barany¹, Paul R Hansen²

Affiliations

¹ Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
² Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.

Abstract

The international peptide community rejoiced when one of its most distinguished members, Morten Meldal of Denmark, shared the 2022 Nobel Prize in Chemistry. In fact, the regiospecific solid-phase "copper(I)-catalyzed 1,3-dipolar cycloaddition of terminal alkynes to azides" (CuACC) reaction-that formed the specific basis for Meldal's recognition-was reported first at the 17^th American Peptide Symposium held in San Diego in June 2001. The present perspective outlines intertwining conceptual and experimental threads pursued concurrently in Copenhagen and Minneapolis, sometimes by the same individuals, that provided context for Meldal's breakthrough discovery. Major topics covered include orthogonality in chemistry; the dithiasuccinoyl (Dts) protecting group for amino groups in α-amino acids, carbohydrates, and monomers for peptide nucleic acids (PNA); and poly(ethylene glycol) (PEG)-based solid supports such as PEG-PS, PEGA, and CLEAR [and variations inspired by them] for solid-phase peptide synthesis (SPPS), solid-phase organic synthesis (SPOS), and combinatorial chemistry that can support biological assays in aqueous media.

Keywords: dithiasuccinoyl (Dts) protection of amines; glycopeptide synthesis; orthogonality in chemistry; poly(ethylene glycol) (PEG)-based supports; solid-phase peptide synthesis (SPPS).

MeSH terms

Alkynes / chemistry
Amino Acids
Azides / chemistry
Click Chemistry
Humans
Peptide Nucleic Acids* / chemistry
Peptides* / chemistry

Substances

Peptides
Peptide Nucleic Acids
Amino Acids
Azides
Alkynes

Grants and funding

Preparation of this perspective (2023) did not require external funding. During the 1980s and 1990s when much of the work described herein was undertaken, GB’s Minneapolis laboratory was generously supported by National Institutes of Health (NIH), grants GM 28934, 42722, and 51628, as well as the Chicago Community Trust (Searle Scholars program), among others. PRH’s graduate studies in Minneapolis were supported in part by the Danish Research Academy.