1.Examination of acylated 4-aminopiperidine-4-carboxylic acid residues in the phosphotyrosyl+1 position of Grb2 SH2 domain-binding tripeptides.
Kang SU1, Choi WJ, Oishi S, Lee K, Karki RG, Worthy KM, Bindu LK, Nicklaus MC, Fisher RJ, Burke TR Jr. J Med Chem. 2007 Apr 19;50(8):1978-82. Epub 2007 Mar 20.
A 4-aminopiperidine-4-carboxylic acid residue was placed in the pTyr+1 position of a Grb2 SH2 domain-binding peptide to form a general platform, which was then acylated with a variety of groups to yield a library of compounds designed to explore potential binding interactions, with protein features lying below the betaD strand. The highest affinities were obtained using phenylethyl carbamate and phenylbutyrylamide functionalities.
2.Intramolecular Rearrangement of α-Amino Acid Amide Derivatives of 2-Aminobenzothiazoles.
Pelletier JC1, Velvadapu V1, McDonnell ME1, Wrobel JE1, Reitz AB1. Tetrahedron Lett. 2014 Jul 23;55(30):4193-4195.
We have found that α-amino acid amide derivatives of 2-aminobenzothiazoles undergo a time-dependent, thermal rearrangement in which the amine group attacks the 2-position carbon of the thiazole ring to form a 5,5-spiro ring system. This is followed by sulfur leaving and air oxidation to the corresponding symmetrical disulfide. The isolated yields of such products are quite high (>70%) if there is conformational bias to further promote the intramolecular reaction such as for the 2-aminobenzothiazole amides derived from proline or 4-aminopiperidine-4-carboxylic acid. This rearrangement has not been described previously for α-amino acid amide derivatives of 2-aminobenzothiazoles. However, a related reaction involving 2-semicarbazido benzothiazoles has been recently reported.
3.Oligo(4-aminopiperidine-4-carboxylic acid): an unusual basic oligopeptide with an acid-induced helical conformation.
Cho JI1, Tanaka M, Sato S, Kinbara K, Aida T. J Am Chem Soc. 2010 Sep 29;132(38):13176-8. doi: 10.1021/ja106118w.
In sharp contrast with helical polypeptides carrying basic side chains, Api(8), a basic oligopeptide containing the non-natural achiral amino acid 4-aminopiperidine-4-carboxylic acid (Api), adopts a helical conformation only in acidic media. Alkaline titration of a protonated Api(8) oligomer appended with a leucine derivative at its N-terminus showed that disruption of its helical conformation occurs in a pH range of 7-10. NMR studies indicated that the piperidine groups in Api(8), when nonprotonated, possibly interact with the proximal amide protons in the peptide backbone and hamper the formation of the H-bonding network responsible for the helical conformation. The helical structure is induced not only by protonation but also by acylation of the piperidine groups.
