Secondary Structural Preferences of 2,2-Disubstituted Pyrrolidine-4-carboxylic Acid Oligomers:  β-Peptide Foldamers that Cannot Form Internal Hydrogen Bonds

• Published in: Journal of the American Chemical Society Vol. 125; no. 30; pp. 9035 - 9037
• Main Authors: Huck, Bayard R, Fisk, John D, Guzei, Ilia A, Carlson, Heather A, Gellman, Samuel H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 30.07.2003; Amer Chemical Soc
• Subjects: Aminoacid polymers; Applied sciences; Biological and medical sciences; Carboxylic Acids - chemistry; Chemistry; Chemistry, Multidisciplinary; Circular Dichroism; Conformational dynamics in molecular biology; Dimerization; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Hydrogen Bonding; Models, Molecular; Molecular biophysics; Nuclear Magnetic Resonance, Biomolecular; Oligopeptides - chemistry; Physical Sciences; Physicochemistry of polymers; Protein Folding; Protein Structure, Secondary; Pyrrolidines - chemistry; Science & Technology; Synthetic biopolymers; SIDE-CHAINS; PROLINE OLIGOPEPTIDES; CD; CIRCULAR-DICHROISM; STABILITY; SEQUENCE; CONFORMATION; ABSORPTION; POLYPEPTIDES; Five membered ring; Oligomerization; Molecular structure; Nitrogen heterocycle; Conformational dynamics; Overhauser effect; Molecular interaction; Polyaminoacid; NMR spectrometry; Secondary structure; Conformational changes; Aminoacid polymer; Pyrrolidine derivatives
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja034561c

We examine a new class of β-peptides, 2,2-disubstituted pyrrolidine-4-carboxylic acid oligomers, and show that they manifest discrete conformational preferences despite the impossibility of internal hydrogen bonding. Numerous β-peptide families have been described that display specific secondary structural preferences, but all of the conformations characterized in detail so far have contained internal hydrogen bonds. Internal hydrogen bonding is observed within the most common secondary structures of conventional peptides as well. Identifying foldamers in which shape control is independent of hydrogen bonding is significant in two ways. At a fundamental level, foldamers in this small but growing class are interesting because their shapes are controlled by distinctive networks of noncovalent forces. At a practical level, non-hydrogen bonded foldamers may be useful in biomedical applications because the low intrinsic polarity of their backbones may promote bioavailability.