Macrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids

Improving the sustainability of synthesis is a major goal in green chemistry, which has been greatly aided by the development of asymmetric transition metal catalysis. Recent advances in asymmetric catalysis show that the ability to control the coordination sphere of substrates can lead to improveme...

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Autores principales:	Richard C. Brewster, Irati Colmenero Labeaga, Catriona E. Soden, Amanda G. Jarvis
Formato:	article
Lenguaje:	EN
Publicado:	The Royal Society 2021
Materias:	cyclic peptides copper catalysis peptide macrocyclization peptide cyclase 1 (PCY1) asymmetric ligand design metallopeptides Science Q
Acceso en línea:	https://doaj.org/article/2b5790923bd7494981b9dfdc915d1510
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spelling	oai:doaj.org-article:2b5790923bd7494981b9dfdc915d15102021-11-12T13:51:47ZMacrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids10.1098/rsos.2110982054-5703https://doaj.org/article/2b5790923bd7494981b9dfdc915d15102021-11-01T00:00:00Zhttps://royalsocietypublishing.org/doi/10.1098/rsos.211098https://doaj.org/toc/2054-5703Improving the sustainability of synthesis is a major goal in green chemistry, which has been greatly aided by the development of asymmetric transition metal catalysis. Recent advances in asymmetric catalysis show that the ability to control the coordination sphere of substrates can lead to improvements in enantioselectivity and activity, in a manner resembling the operation of enzymes. Peptides can be used to mimic enzyme structures and their secondary interactions and they are easily accessible through solid-phase peptide synthesis. Despite this, cyclic peptides remain underexplored as chiral ligands for catalysis due to synthetic complications upon macrocyclization. Here, we show that the solid-phase synthesis of peptides containing metal-binding amino acids, bipyridylalanine (1), phenyl pyridylalanine (2) and N,N-dimethylhistidine (3) can be combined with peptide macrocylization using peptide cyclase 1 (PCY1) to yield cyclic peptides under mild conditions. High conversions of the linear peptides were observed (approx. 90%) and the Cu-bound cyclo(FSAS(1)SSKP) was shown to be a competent catalyst in the Friedel-Crafts/conjugate addition of indole. This study shows that PCY1 can tolerate peptides containing amino acids with classic inorganic and organometallic ligands as side chains, opening the door to the streamlined and efficient development of cyclic peptides as metal ligands.Richard C. BrewsterIrati Colmenero LabeagaCatriona E. SodenAmanda G. JarvisThe Royal Societyarticlecyclic peptidescopper catalysispeptide macrocyclizationpeptide cyclase 1 (PCY1)asymmetric ligand designmetallopeptidesScienceQENRoyal Society Open Science, Vol 8, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cyclic peptides copper catalysis peptide macrocyclization peptide cyclase 1 (PCY1) asymmetric ligand design metallopeptides Science Q
spellingShingle	cyclic peptides copper catalysis peptide macrocyclization peptide cyclase 1 (PCY1) asymmetric ligand design metallopeptides Science Q Richard C. Brewster Irati Colmenero Labeaga Catriona E. Soden Amanda G. Jarvis Macrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids
description	Improving the sustainability of synthesis is a major goal in green chemistry, which has been greatly aided by the development of asymmetric transition metal catalysis. Recent advances in asymmetric catalysis show that the ability to control the coordination sphere of substrates can lead to improvements in enantioselectivity and activity, in a manner resembling the operation of enzymes. Peptides can be used to mimic enzyme structures and their secondary interactions and they are easily accessible through solid-phase peptide synthesis. Despite this, cyclic peptides remain underexplored as chiral ligands for catalysis due to synthetic complications upon macrocyclization. Here, we show that the solid-phase synthesis of peptides containing metal-binding amino acids, bipyridylalanine (1), phenyl pyridylalanine (2) and N,N-dimethylhistidine (3) can be combined with peptide macrocylization using peptide cyclase 1 (PCY1) to yield cyclic peptides under mild conditions. High conversions of the linear peptides were observed (approx. 90%) and the Cu-bound cyclo(FSAS(1)SSKP) was shown to be a competent catalyst in the Friedel-Crafts/conjugate addition of indole. This study shows that PCY1 can tolerate peptides containing amino acids with classic inorganic and organometallic ligands as side chains, opening the door to the streamlined and efficient development of cyclic peptides as metal ligands.
format	article
author	Richard C. Brewster Irati Colmenero Labeaga Catriona E. Soden Amanda G. Jarvis
author_facet	Richard C. Brewster Irati Colmenero Labeaga Catriona E. Soden Amanda G. Jarvis
author_sort	Richard C. Brewster
title	Macrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids
title_short	Macrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids
title_full	Macrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids
title_fullStr	Macrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids
title_full_unstemmed	Macrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids
title_sort	macrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids
publisher	The Royal Society
publishDate	2021
url	https://doaj.org/article/2b5790923bd7494981b9dfdc915d1510
work_keys_str_mv	AT richardcbrewster macrocylasesassynthetictoolsforligandsynthesisenzymaticsynthesisofcyclicpeptidescontainingmetalbindingaminoacids AT iraticolmenerolabeaga macrocylasesassynthetictoolsforligandsynthesisenzymaticsynthesisofcyclicpeptidescontainingmetalbindingaminoacids AT catrionaesoden macrocylasesassynthetictoolsforligandsynthesisenzymaticsynthesisofcyclicpeptidescontainingmetalbindingaminoacids AT amandagjarvis macrocylasesassynthetictoolsforligandsynthesisenzymaticsynthesisofcyclicpeptidescontainingmetalbindingaminoacids
_version_	1718430360448008192

Macrocylases as synthetic tools for ligand synthesis: enzymatic synthesis of cyclic peptides containing metal-binding amino acids

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