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6-Strand to Stable 10/12 Helix Conformational Switch by Incorporating Flexible ß-hGly in the Homooligomers of Camphor Derived ß-Amino Acid: NMR and X-Ray Crystallographic Evidence.
Sukumar, Genji; Nayani, Kiranmai; Mainkar, Prathama S; Prashanth, Jupally; Sridhar, Balasubramanian; Sarma, Akella V S; Bharatam, Jagadeesh; Chandrasekhar, Srivari.
Afiliação
  • Sukumar G; Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
  • Rahul; Department of Chemistry, Adikavi Nannaya University, Rajamahendravaram, Andhra Pradesh, 533296, India.
  • Nayani K; Centre for NMR, Department of Analytical & Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
  • Mainkar PS; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
  • Prashanth J; Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
  • Sridhar B; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
  • Sarma AVS; Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
  • Bharatam J; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
  • Chandrasekhar S; Centre for X-ray Crystallography, Department of Analytical & Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
Angew Chem Int Ed Engl ; 63(22): e202403321, 2024 05 27.
Article em En | MEDLINE | ID: mdl-38482551
ABSTRACT
Rational design of unnatural amino acid building blocks capable of stabilizing predictable secondary structures similar to protein fragments is pivotal for foldamer chemistry/catalysis. Here, we introduce novel ß-amino acid building blocks [1S,2R,4R]exoCDA and [1S,2S,4R]endoCDA, derived from the abundantly available R(+)-camphor, which is traditionally known for its medicinal value. Further, we demonstrate that the homooligomers of exoCDA adopt 6-strand conformation, which switches to a robust 10/12-helix simply by inserting flexible ß-hGly spacer at alternate positions (1 1 ß-hGly/exoCDA heterooligomers), as evident by DFT-calculations, solution-state NMR spectroscopy and X-ray crystallography. To the best of our knowledge, this is the first example of crystalline-state structure of left-handed 10/12-mixed helix, that is free from the conventional approach of employing ß-amino acids of either alternate chirality or alternate ß2/ß3 substitutions, to access the 10/12-helix. The results also show that the homooligomers of heterochiral exoCDA don't adopt helical fold, instead exhibit banana-shaped strands, whereas the homodimers of the other diastereomer endoCDA, nucleate 8-membered turns. Furthermore, the homo-exoCDA and hetero-[ß-hGly-exoCDA] oligomers are found to exhibit self-association properties with distinct morphological features. Overall, the results offer new possibilties of constructing discrete stable secondary and tertiary structures based on CDAs, which can accommodate flexible residues with desired side-chain substitutions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cânfora / Aminoácidos Idioma: En Revista: Angew Chem Int Ed Engl Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Índia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cânfora / Aminoácidos Idioma: En Revista: Angew Chem Int Ed Engl Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Índia