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Conformational Analysis of β-Peptides: Structure, Stability, and Biological Implications

This article explores the conformational properties of β-peptides, highlighting their unique structural features and stability compared to α-peptides. It discusses various studies focused on the folding preferences of β-peptides, particularly their propensity for secondary structures like the 314-helix and hairpin formations. Insights into their bioavailability, metabolic stability, and interactions with biological targets, including their potential as therapeutics, are also presented. Relevant literature from the field, showcasing advancements in β-peptide research, will be referenced.

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Conformational Analysis of β-Peptides: Structure, Stability, and Biological Implications

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  1. Conformational Analysis of -Peptides For a recent review, see: Chemistry & Biodiversity, 2004, 1, 1111. (available as PDF on Chem. 206 website)

  2. Reviews: Biopolymers (Peptide Science) 2004, 76, 206-243 Tetrahedron 2004, 60, 7455-7506 Chemistry&Biodiversity 2004, 1, 1111-1239 J.Peptide Res.2005, 65, 229-260 Biopolymers (Peptide Science) 2006, 84, 23

  3. The b-peptidic sheet (S) (R) no gem-disubstituted -amino acids! ACIE 1999, 38, 1595

  4. Boc-3-HVal-3-HAla-3-HLeu-OMe in the Crystal HCA 1996, 79, 913

  5. Comparison of Hairpin Structures of a- and b-Peptides N C a H unpolar H H A1,3-effect b N C H + - polar • Helv. Chim. Acta 89, 361 - 403 (2006) polar + -

  6. The (M)-314-helix (S) (S) i (S) (R) i+3 no gem-disubstituted -amino acids! (S) (S) (S) (S)

  7. NMR-Solution Structure of a “Mixed” b/a-Tridecapeptide b-peptidic segment (6 residues) a-peptidic segment (7 residues) b-Peptide: 314-(M)-Helix a-Peptide: poor propensity for a stable secondary structure ……a demonstration of the large difference of folding preference between of b- and a-peptides R. I. Mathad, ETH Zuerich

  8. ADME Investigations (14C2)Ac-3hTyr-(R)Trp-3hLys-3hThr-OH (tetramer) p.o. bioavailable (25% after 15 min; 2mg/kg) totally cleared from body in 4 days excretion through feces and urine •15nM affinity to somatostatin hsst4 receptor metabolically stable H-3hAla-3hLys-3hPhe-3hAla-3hLys-(14C2)3hPhe- -3hAla-3hLys-3hPheOH (nonamer) no p.o. bioavailability 50% cleared from body 7 days after i.v. (5mg/kg) excretion through feces and urine, not bile •inhibitor of SRB1 enzyme in CaCo-2 cells metabolically stable (14C2)Ac-(3hArg)8-NH2 (octamer) no p.o. bioavailability totally cleared from body 1 day after p.o. <2 % clearance in 7 days after i.v. (1mg/kg) redistribution in body over time •cell-penetrating HeLa, keratinocyte cells metabolically stable Chemistry & Biodiversity 2007, 4, 1413 Biopharm. Drug Dispos. 2002, 23, 251 CBD 2004, 1, 1812

  9. Structure of Medium-Size Rings

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