Polar Hinges as Functionalized Conformational Constraints in (Bi)cyclic Peptides

Chembiochem : a European Journal of Chemical Biology
Helmus van de LangemheenRob M J Liskamp

Abstract

Two polar hinges for cyclization of peptides have been developed, leading to bicyclic peptides and cyclized peptides with improved solubility and biological activity. Increasingly, we note that a good aqueous solubility of peptides is an absolute prerequisite, not only to allow handling and purification of our target peptides but also being crucial for biological activity characteristics. Compared to earlier hinges, the 1,1',1"-(1,3,5-triazinane-1,3,5-triyl)tris(2-bromoethanone) (TATB) and 2,4,6-tris(bromomethyl)-s-triazine (TBMT), each containing three nitrogen atoms are structurally similar but chemically very different. Both were accessible in a one-step fashion from bromoacetonitrile. TATB and TBMT are very suitable for the preparation of more soluble bicyclic peptides. Azide-modified TATB and TBMT derivatives provide hinges for the preparation of cyclized peptides for incorporation on scaffolds to afford protein mimics.

References

Oct 25, 2003·The Journal of Organic Chemistry·Pasi Virta, Harri Lönnberg
May 16, 2008·Journal of the American Chemical Society·Yusuke SakoHiroaki Suga
Jun 2, 2009·Nature Chemical Biology·Christian HeinisGreg Winter
Feb 7, 2012·ACS Chemical Biology·Alessandro AngeliniChristian Heinis
Apr 12, 2012·Chembiochem : a European Journal of Chemical Biology·Shiyu ChenChristian Heinis
Sep 1, 2012·Chemical Communications : Chem Comm·Gwenn E MulderRob M J Liskamp
Oct 20, 2012·The Journal of Organic Chemistry·Helmus van de LangemheenRob M J Liskamp
Mar 8, 2013·Organic & Biomolecular Chemistry·Gwenn E MulderRob M J Liskamp
Jan 24, 2014·Angewandte Chemie·Shiyu ChenChristian Heinis
Apr 9, 2014·Organic Letters·Helmus van de LangemheenRob M J Liskamp
May 23, 2014·Organic & Biomolecular Chemistry·Helmus van de LangemheenRob M J Liskamp
Jul 11, 2014·The Journal of Organic Chemistry·Antonio HerreraRoberto Martínez-Alvarez
Oct 8, 2014·Angewandte Chemie·Timothy A HillDavid P Fairlie
Jan 13, 2015·Chemical Communications : Chem Comm·Laura Nevola, Ernest Giralt
May 20, 2015·ACS Chemical Biology·Vanessa BaeriswylChristian Heinis

Citations

Jan 28, 2020·Journal of Peptide Science : an Official Publication of the European Peptide Society·Theodorus J MeulemanRob M J Liskamp
Mar 5, 2021·Bioconjugate Chemistry·Caitlin M CarmodySam R Nugen
Jan 15, 2021·Chembiochem : a European Journal of Chemical Biology·Kasper K SørensenKnud J Jensen
Sep 5, 2020·European Journal of Medicinal Chemistry·Clara DavoineLionel Pochet

Related Concepts

Cyclic Peptides
Biomimetics
Nitrogen
Peptides
Carmustine/Triazinate
S-triazine Compound Metabolic Process
Pharmacologic Substance
UQCRH gene
CYP2C19*1 Allele
1,3,5-trihydroxy-1,3,5-triazinane-2,4,6-trione

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