Self‐Synthesizing Models of Helical Proteins Based on Aromatic Disulfide Chemistry

Abstract

A new method of synthesis of peptide conjugates with aromatic moieties substituted with two sulfhydryl groups at 1,3-positions is proposed. Amphiphilic peptides derivatized in such a way under oxidative conditions spontaneously form cyclic, covalent trimers and tetramers dominated by α-helical conformations. The tendency to form tri- or tetrahelical bundles depends on sequences of the peptides and on the oxidation conditions, pH, and additives.

Alkyl Thiocyanurates as Thioester Mimetics. Transthioesterification and Ligation Reactions with High Potential in Dynamic Covalent Chemistry

“…Then the nitrogen atoms of the triazine ring remain the only hydrogen bond acceptors in the final molecule and stay Scheme 1. Similarities in the Reactivity of Carboxylic Acid Thioesters (1) We carried out the reaction at a higher temperature in TEAB buffer to see if it is possible to substitute more than one thioglycolic acid residue with 5 equivalents of cysteamine. Up to 50 °C, we observed the selective formation of DMT-(AcOH) 2 (cysteamine) while starting from 60 °C the disubstituted MMT(AcOH) (cysteamine) 2 started to rise, giving the monomercaptotriazine (MMT) as the main product at 90 °C.…”

“…In one of our previous works, we described the preparation of peptides conjugated with 1,3,5-trimercaptobenzene by one of its sulfhydryl groups, followed by oxidation, giving dynamic libraries of template-assembled synthetic proteins (TASP) molecules . In the same work, we described unsuccessful efforts to synthesize the triaza-analogues of those compounds.…”

Peptide and Peptidomimetic Assemblies in Dynamic Combinatorial Chemistry

“…Going beyond the coiled‐coil assembly, Stefanowicz and co‐workers have recently developed tri‐ and tetra‐helical bundles, based on the use of an aromatic template, to pack amphipatic α‐helices by DCvC through, disulfide bridge formation (Figure 8c). [93] …”

Mismatched covalent and noncovalent templating leads to large coiled coil-templated macrocycles

“…We and others have previously reported using this approach to create novel structures. [28][29][30][31][32][33][34][35][36][37][38][39][40][41] Among these, globular-like assemblies have been discovered by coupling b-turns, 28,29,31 and nucleobases, with DCC while bril formation has also been observed with short unstructured peptides and b-strand-templated DCLs via nonspecic hydrophobic interactions and b-sheet assembly, respectively. [32][33][34][35][36][37] However, the coupling of DCC with peptides that are designed to form discrete quaternary structures has only been minimally explored.…”

“…[32][33][34][35][36][37] However, the coupling of DCC with peptides that are designed to form discrete quaternary structures has only been minimally explored. 38,39,42 To this end, we sought to investigate how the coupling of a DCC building block to a peptide that favors a discrete quaternary structure inuences the balance between formation of covalent bonds between DCC monomers and noncovalent interactions between peptides to give biomimetic peptide assemblies. Herein, we describe the coupling of a series of peptides, which are designed to form homodimeric a-helical coiled coils, with a DCC building block that favors cyclic trimer and tetramer formation via reversible covalent bond formation (Fig.…”