A Multiple Multicomponent Approach to Chimeric Peptide-Peptoid Podands

• Published in: Chemistry : a European journal Vol. 19; no. 20; pp. 6417 - 6428
• Main Authors: Rivera, Daniel G., León, Fredy, Concepción, Odette, Morales, Fidel E., Wessjohann, Ludger A.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 10.05.2013; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Amino Acids - chemistry; Arrays; Assembly; Binding; Branched; Catalysis; Chemistry; Chemistry, Multidisciplinary; Combinatorial analysis; Magnetic Resonance Spectroscopy; Molecular Structure; multicomponent reactions; Peptides; Peptides - chemistry; Peptoids - chemistry; Physical Sciences; Platforms; Receptors; Science & Technology; steroids; Steroids - chemistry; supramolecular chemistry; synthetic receptors; Tracking; Ugi reaction; multicomponent reactions; Ugi reaction; BUILDING-BLOCKS; COMBINATORIAL LIBRARIES; N-ISOBUTYLGLYCINE NLEU; SEQUENCE-SELECTIVE BINDING; HYBRID MACROCYCLES; synthetic receptors; steroids; CONFORMATIONAL-ANALYSIS; COLLAGEN-BASED STRUCTURES; supramolecular chemistry; ARTIFICIAL RECEPTORS
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201201591

The success of multi‐armed, peptide‐based receptors in supramolecular chemistry traditionally is not only based on the sequence but equally on an appropriate positioning of various peptidic chains to create a multivalent array of binding elements. As a faster, more versatile and alternative access toward (pseudo)peptidic receptors, a new approach based on multiple Ugi four‐component reactions (Ugi‐4CR) is proposed as a means of simultaneously incorporating several binding and catalytic elements into organizing scaffolds. By employing α‐amino acids either as the amino or acid components of the Ugi‐4CRs, this multiple multicomponent process allows for the one‐pot assembly of podands bearing chimeric peptide–peptoid chains as appended arms. Tripodal, bowl‐shaped, and concave polyfunctional skeletons are employed as topologically varied platforms for positioning the multiple peptidic chains formed by Ugi‐4CRs. In a similar approach, steroidal building blocks with several axially‐oriented isocyano groups are synthesized and utilized to align the chimeric chains with conformational constrains, thus providing an alternative to the classical peptido‐steroidal receptors. The branched and hybrid peptide–peptoid appendages allow new possibilities for both rational design and combinatorial production of synthetic receptors. The concept is also expandable to other multicomponent reactions. Fast track to podands: The rapid and highly versatile assembly of podands with linear or branched oligopeptidic arms can be achieved in one pot through multiple Ugi reactions involving a variety of flexible or preorganizing core moieties (see figure).