β-Amino acid facilitates macrocyclic ring closure in a combinatorial library

Life as we know it would not exist without the ability of protein sequences to bind metal ions. Transition metals, in particular, play essential roles in a wide range of structural and catalytic functions. The ubiquitous occurrence of metalloproteins in all organisms leads one to ask whether metal binding is an evolved trait that occurred only rarely in ancestral sequences, or alternatively, whether it is an innate property of amino acid sequences, occurring frequently in unevolved sequence space. To address this question, we studied 52 proteins from a combinatorial library of novel sequences designed to fold into 4-helix bundles. Although these sequences were neither designed nor evolved to bind metals, the majority of them have innate tendencies to bind the transition metals copper, cobalt, and zinc with high nanomolar to low-micromolar affinity.

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Concise Synthesis of Macrocycles by Multicomponent Reactions

Synthesis ◽

10.1055/s-0036-1590946 ◽

2018 ◽

Vol 50 (05) ◽

pp. 1027-1038 ◽

Cited By ~ 2

Author(s):

Alexander Dömling ◽

Eman Abdelraheem ◽

Samad Khaksar

Keyword(s):

Amino Acid ◽

Multicomponent Reaction ◽

Ring Opening ◽

Multicomponent Reactions ◽

Reaction Pathway ◽

Ring Closure ◽

Side Chains ◽

Reaction Sequence ◽

Cyclic Anhydride

A short reaction pathway was devised to synthesize a library of artificial 18–27-membered macrocycles. The five-step reaction sequence involves ring opening of a cyclic anhydride with a diamine, esterification, coupling with an amino acid isocyanide, saponification, and, finally, macro-ring closure using an Ugi or, alternatively, a Passerini multicomponent reaction. Three out of the five steps allow for the versatile introduction of linker elements, side chains, and substituents with aromatic, heteroaromatic, and aliphatic character. The versatile pathway is described for 15 different target macrocycles on a mmol scale. Artificial macrocycles have recently become of great interest due to their potential to bind to difficult post-genomic targets.

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ChemInform Abstract: Towards the Synthesis of Epothilone A: Enantioselective Preparation of the Thiazole Sidechain and Macrocyclic Ring Closure.

ChemInform ◽

10.1002/chin.199733212 ◽

2010 ◽

Vol 28 (33) ◽

pp. no-no

Author(s):

R. E. TAYLOR ◽

J. D. HALEY

Keyword(s):

Ring Closure ◽

Macrocyclic Ring ◽

Epothilone A

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Cleavage Reactions of Oxazolin-5-ones Reactions with 4-Substituted-2-aryl-2-oxazolin-5-ones

Zeitschrift für Naturforschung B ◽

10.1515/znb-1978-1021 ◽

1978 ◽

Vol 33 (10) ◽

pp. 1145-1149 ◽

Cited By ~ 3

Author(s):

Nazmi Kassab ◽

Abdul Harhash ◽

Said Elbahaii

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Alkaline Medium ◽

Ring Closure ◽

Ring Cleavage ◽

Aminobenzoic Acids ◽

Cleavage Reactions

Abstract The oxazoline ring in 4-arylazo-2-aryl-2-oxazolin-5-ones (1) is converted to triazolyl-carbonyl amino acids 2, 4 and 6 by the nucleophiles glycine, anthranilic and p-aminobenzoic acids, respectively. The arylidene derivatives 3 of 2-triazolyl-2-oxazolin-5-one were obtained. Triazolylbenzoxazinones 5, were obtained by the ring closure of the amino acid 4.Grignard's reagent effected ring cleavage of the oxazolinone ring in 4-cinnamylidene-2-aryl-2-oxazolin-5-ones yielding the carbinols 8, the latter cyclizes either in acidic or alkaline medium to afford either benzotropilidenes or oxazolines, respectively.

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