144085-23-4Relevant articles and documents
Design, synthesis, and in vitro activity of peptidomimetic inhibitors of myeloid differentiation factor 88
Fantò, Nicola,Gallo, Grazia,Ciacci, Andrea,Semproni, Mauro,Vignola, Davide,Quaglia, Marco,Bombardi, Valentina,Mastroianni, Domenico,Zibella, M. Pia,Basile, Giancarlo,Sassano, Marica,Ruggiero, Vito,De Santis, Rita,Carminati, Paolo
, p. 1189 - 1202 (2008/09/20)
We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide AC-RDVLPGT-NH2, belonging to the Toll/IL-1 receptor (TIR) domain of the adaptor protein MyD88 and effective in inhibiting its homodimerization. The a
A highly practical RCM approach towards a molecular building kit of spirocyclic reverse turn mimics
Bittermann, Holger,Boeckler, Frank,Einsiedel, Juergen,Gmeiner, Peter
, p. 6315 - 6322 (2008/09/19)
The development of privileged molecular scaffolds efficiently mimicking reverse turn motifs and thus increasing both binding and selectivity and enabling the elucidation of the bio-active conformation of a natural peptide has attracted remarkable interest. The frequent occurrence of proline in various turn patterns initiated the design of proline-based reverse turn mimetics. As a structural hybridization of a highly potent type VI β-turn inducer 1 with saturated spirocyclic lactams 3 efficiently mimicking type II β turns, we developed a versatile synthetic route towards unsaturated spirocyclic lactams of type 2, when Seebach's self-reproduction of chirality methodology was combined with a peptide coupling reaction and Grubbs' ring-closing metathesis. By this means, a variety of model peptides with six- up to nine-membered lactam rings were accessible following a uniform pathway. Introduction of suitably protected templates into solid-phase peptide synthesis gave rise to unsaturated spirocyclic analogues of the naturally occurring neuropeptide neurotensin. Spectroscopic investigations as well as DFT calculations on a high level of theory revealed a remarkable dependence of the reverse-turn inducing potency on the ring size. While the secondary structure of the unsaturated spirocyclic ε-lactam 12 closely agrees with the reference γlactam 3a, the unsaturated δ-lactam 11 serves as an extraordinarily potent β-turn inducer which is even superior to β-lactams of type 3b. The eight-membered unsaturated spirocyclic lactam 13 adopts a conformation almost ideally matching the prerequisites for a canonical type II β turn with the highest stability of the whole series. In contrast, the nine-membered spirolactam 14 represents a scaffold with a high conformational flexibility.
Design, synthesis, and dopamine receptor modulating activity of spiro bicyclic peptidomimetics of L-prolyl-L-leucyl-glycinamide
Khalil, Ehab M.,Ojala, William H.,Pradhan, Ashish,Nair, Venugopalan D.,Gleason, William B.,Mishra, Ram K.,Johnson, Rodney L.
, p. 628 - 637 (2007/10/03)
In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of
