1235568-29-2Relevant academic research and scientific papers
Synthesis of GSK3β mimetic inhibitors of Akt featuring a novel extended dipeptide surrogate
Ranatunga, Sujeewa,Del Valle, Juan R.
scheme or table, p. 7166 - 7169 (2012/01/15)
Akt is a cardinal nodal point in PI3K signaling pathway and confers resistance to apoptosis through inactivation of regulatory substrates such as GSK3β. Efforts to inhibit the kinase activity of Akt have largely focused on targeting the ATP-binding domain
Synthesis and conformational analysis of bicyclic extended dipeptide surrogates
Ranatunga, Sujeewa,Liyanage, Wathsala,Del Valle, Juan R.
experimental part, p. 5113 - 5125 (2010/10/04)
(Figure presented) Regio- and diastereoselective reactions of a homoproline enolate enable the synthesis of novel extended dipeptide surrogates. Bicyclic carbamate 9 and fused β-lactam scaffold 11 were prepared from l-pyroglutamic acid via substrate-controlled electrophilic azidation. Synthesis of orthogonally protected hexahydropyrrolizine, hexahydropyrrolizinone, and hexahydropyrroloazepinone dipeptide surrogates relied on allylation of proline derivative 5, followed by Curtius rearrangement to introduce the N-terminal carbamate group. A total of six azabicycloalkane derivatives were evaluated for conformational mimicry of extended dipeptides by a combination of X-ray diffraction and molecular modeling. Analysis of putative backbone dihedral angles and N- to C-terminal dipeptide distances indicate that compounds (α′S)-14b and 21 approximate the conformation of dipeptides found in β-sheets, while tripeptide mimic 28 is also highly extended in the solid state. Structural data suggest that ring size and relative stereochemistry have a profound effect on the ability of these scaffolds to act as β-strand mimetics and should inform the design of related conformational probes.
