An Effective Strategy for Stabilizing Minimal Coiled Coil Mimetics

التفاصيل البيبلوغرافية
العنوان: An Effective Strategy for Stabilizing Minimal Coiled Coil Mimetics
المؤلفون: Paramjit S. Arora, Michael G. Wuo, Andrew B. Mahon
المصدر: Journal of the American Chemical Society
بيانات النشر: American Chemical Society, 2015.
سنة النشر: 2015
مصطلحات موضوعية: Coiled coil, Models, Molecular, Protein Conformation, Dimer, Communication, Molecular Mimicry, Molecular Sequence Data, Ionic bonding, Proteins, General Chemistry, Biochemistry, Catalysis, Crystallography, chemistry.chemical_compound, Colloid and Surface Chemistry, Protein structure, chemistry, Covalent bond, Biophysics, Conformational stability, Amino Acid Sequence, Linker, Peptide sequence
الوصف: Coiled coils are a major motif in proteins and orchestrate multimerization of various complexes important for biological processes. Inhibition of coiled coil-mediated interactions has significant biomedical potential. However, general approaches that afford short peptides with defined coiled coil conformation remain elusive. We evaluated several strategies to stabilize minimal helical bundles, with the dimer motif as the initial focus. A stable dimeric scaffold was realized in a synthetic sequence by replacing an interhelical ionic bond with a covalent bond. Application of this strategy to a more challenging native protein–protein interaction (PPI) suggested that an additional constraint, a disulfide bond at the internal a/d′ position along with a linker at the e/e′ position, is required for enhanced conformational stability. We anticipate the coiled coil stabilization methodology described herein to yield new classes of modulators for PPIs.
اللغة: English
تدمد: 1520-5126
0002-7863
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::39f3fca29cc8f1059e4d23b54b111e5aTest
http://europepmc.org/articles/PMC4577959Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....39f3fca29cc8f1059e4d23b54b111e5a
قاعدة البيانات: OpenAIRE