840540-56-9Relevant academic research and scientific papers
Novel peptides comprising furanoid sugar amino acids for the treatment of cancer
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, (2010/02/10)
Anticancer peptides which incorporate furanoid sugar amino acids and compositions made using these peptides are described. Methods for synthesis of the peptides and for preparing the furanoid sugar amino acids are disclosed. The peptides and compositions made using the peptides have pharmacological applications of these peptides especially in the treatment and prevention of cancer and tumors.
Cyclic homooligomers of furanoid sugar amino acids
Chakraborty,Srinivasu,Bikshapathy,Nagaraj,Vairamani,Kumar, S. Kiran,Kunwar
, p. 6257 - 6263 (2007/10/03)
Cyclic homooligomers of mannose-derived furanoid sugar amino acid 1 [H-Maa(Bn2)-OH] were synthesized by using BOP reagent in the presence of DIPEA under dilute conditions that converted the sugar amino acid monomer directly into its cyclic homooligomers 3a and 4a. The glucose-based sugar amino acid 2 [H-Gaa(Bn2)-OH] under the same reaction conditions gave a bicyclic lactam 5a as the major product. Cyclic homooligomers of 2 were prepared by cyclizing their linear precursors 6 and 7 leading to the formation of cyclic peptides 8a and 9a, respectively. Conformational analysis by NMR and constrained MD studies revealed that all the cyclic products, 3, 4, 8, and 9, had symmetrical structures. The deprotected cyclic trimer of Maa 3b displayed a conformation in which all the C=O and the N-H bonds of the molecule point in opposite directions. In the deprotected cyclic tetramer of Maa 4b, the COs and NHs were in the plane of the ring with the former pointing to outside and the latter inside the ring. The structure of the cyclic Gaa dimer 8b displayed an unusual six-membered intramolecular hydrogen bond between NHi → C3-Oi-1 and a syn orientation between the C2-H and CO. In this molecule, the C2-hydrogens and the COs can be seen on one side of the ring while the NHs point to the other side. Addition of the bicyclic lactam 5b resulted in the influx of Na+ ions across the lipid bilayer leading to the dissipation of valinomycin-mediated K+ diffusion potential.
Synthesis and structural studies of oligomers of 6-amino-2,5-anhydro-6-deoxy-D-mannonic acid
Chakraborty,Jayaprakash,Srinivasu,Chary,Diwan,Nagaraj,Sankar,Kunwar
, p. 8167 - 8171 (2007/10/03)
A novel cycloetherification process involving a facile 5-exo S(N)2-type ring closure by intramolecular opening of a terminal aziridine ring by a γ-hydroxyl group, led to the stereoselective synthesis of 6-amino-2,5-anhydro-6-deoxy-D-mannonic acid (1). Oligomerization of 1 by solution phase peptide coupling methods gave oligomers 2-5. While most of the oligomers, in either protected or deprotected form, did not show any significant secondary structure, octamer 5 (P = H) exhibited a very strong positive band at 216 nm in its CD spectrum in MeOH and TFE, indicating the possibility of the presence of an ordered structure in solution. Its 1H NMR spectra in various polar solvents, however, failed to produce any distinct dispersion of the amide proton chemical shifts. Compounds 1-5 were found to be inactive in hypoglyceamic tests in rats. (C) 2000 Elsevier Science Ltd.
Synthesis and Conformational Studies of Peptidomimetics Containing Furanoid Sugar Amino Acids and a Sugar Diacid
Chakraborty,Ghosh,Jayaprakas,Sharma,Ravikanth,Diwan,Nagaraj,Kunwar
, p. 6441 - 6457 (2007/10/03)
Furanoid sugar amino acids (1) were synthesized and used as dipeptide isosteres to induce interesting turn structures in small linear peptides. They belong to a new variety of designed hybrid structures that carry both amino and carboxyl groups on rigid furanose sugar rings. Four such molecules, 6-amino-2,5-anhydro-6-deoxy-D-gluconic acid (3, Gaa) and its mannonic (4, Maa), idonic (5, Iaa), and a 3,4-dideoxyidonic (6, ddIaa) congeners were synthesized. The synthesis followed a novel reaction path in which an intramolecular 5-exo SN2 opening of the hexose-derived terminal aziridine ring in 2 by the γ-benzyloxy oxygen with concomitant debenzylation occurred during pyridinium dichromate oxidation of the primary δ-hydroxyl group to carboxyl function, leading to the formation of furanoid sugar amino acid frameworks in a single step. Incorporation of these furanoid sugar amino acids into Leu-enkephalin replacing its Gly-Gly portion gave analogues 8-11. Detailed structural analysis of these molecules by circular dichroism (CD) and various NMR techniques in combination with constrained molecular dynamics (MD) simulations revealed that two of these analogues, 8a and 10a, have folded conformations composed of an unusual nine-membered pseudo β-turn-like structure with a strong intramolecular H-bond between LeuNH → sugarC3-OH. This, in turn, brings the two aromatic rings of Tyr and Phe in close proximity, a prerequisite for biological activities of opioid peptides. The analgesic activities of 8a,b determined by mouse hot-plate and tail-clip methods were similar to that of Leu-enkephalin methyl ester. The syn disposition of the β-hydroxycarboxyl motif on the sugar rings appears to be the driving force to nucleate the observed turn structures in some of these molecules (8 and 10). Repetition of the motif on both sides of a furanose ring resulted in a novel molecular design of sugar diacid, 2,5-anhydro-D-idaric acid (7, Idac). Bidirectional elongation of the diacid moieties of 7 with identical peptide strands led to the formation of a C2-symmetric reverse-turn mimetic 12 which displayed a very ordered structure consisting of identical intramolecular H-bonds at two ends between LeuNH → sugar-OH, the same as in 8 and 10.
