286964-95-2Relevant academic research and scientific papers
Synthesis and conformation of Gly-Gly dipeptides constrained with phenylalanine-like aminocaproic acid linkers.
MacDonald,Vander Velde,Aube
, p. 1653 - 1655 (2000)
[structure: see text] The constraint of dipeptides with linkers derived from 6-aminocaproic acid (Aca) is a useful means of constructing a beta-turn peptidomimetic. The extension of this concept to the mimicry of a tripeptide entails the incorporation of a side chain moiety on either end of the Aca chain. The synthesis and conformational analysis of two exemplary compounds is discussed.
Conjugates of modified cryptophycins and RGD-peptides enter target cells by endocytosis
Nahrwold, Markus,Wei?, Christine,Bogner, Tobias,Mertink, Felix,Conradi, Jens,Sammet, Benedikt,Palmisano, Ralf,Royo Gracia, Soledad,Preu?e, Thomas,Sewald, Norbert
supporting information, p. 1853 - 1864 (2013/05/09)
Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized β2-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.
Synthesis of Cα methylated carboxylic acids: Isosteres of arginine and lysine for use as N-terminal capping residues in polypeptides
Orwig, Kevin S.,Dix, Thomas A.
, p. 7007 - 7009 (2007/10/03)
Replacement of the N-terminal α-amine with the isosteric methyl functionality in bioactive peptides can influence various pharmacokinetic parameters, including hydrophobicity and stability. Cα methylated amino acid analogues are thus of great interest to expand the repertoire of nonnatural synthons available as N-terminal 'capping' residues for peptide-based drug design. Several novel arginine and lysine analogues stereoselectively modified in the Cα position with a methyl group in place of the α-amine were prepared.
Effect of progressive benzyl substitution on the conformations of aminocaproic acid-cyclized dipeptides
MacDonald,Vander Velde,Aube
, p. 2636 - 2642 (2007/10/03)
The constraint of dipeptides into a β-turn conformation can be accomplished by linking the two ends of a standard dipeptide with a linker derived from aminocaproic acid (aca). To elucidate the possibility of using substituted Aca linkers in peptidomimetic design, a series of five macrocycles composed of a monobenzylated Aca linker (containing the benzyl group on each of the five methylene groups of the parent linker) and Gly-gly were synthesized. The requisite linkers were made by regiochemically controlled ring expansion techniques (for substitution on Aca positions C-3, C-4, or C-5), an Evans alkylation route (for C-2), or by chain extension of L-phenylalanal (for C-6). The solution-phase conformations of the macrocycles were examined by Nmr and Cd techniques; in addition, crystal structures of the C-4- and C-6-benzyl-substituted linkers were obtained. Four out of the five macrocycles were found to exist with the dipeptide portion taking up either a type Ii or Ii′ β-turn conformation, but the Gly-gly unit in the compound derived from 4-benzyl-aca did not correspond to one of the standard β-turn types.
