27 research outputs found
Structure-based design of a Cortistatin analogue with immunomodulatory activity in models of inflammatory bowel disease
Full text linkUlcerative colitis and Crohn's disease are forms of inflammatory bowel disease whose incidence and prevalence are increasing worldwide. These diseases lead to chronic inflammation of the gastrointestinal tract as a result of an abnormal response of the immune system. Recent studies positioned Cortistatin, which shows low stability in plasma, as a candidate for IBD treatment. Here, using NMR structural information, we design five Cortistatin analogs adopting selected native Cortistatin conformations in soln. One of them, A5, preserves the anti-inflammatory and immunomodulatory activities of Cortistatin in vitro and in mouse models of the disease. Addnl., A5 displays an increased half-life in serum and a unique receptor binding profile, thereby overcoming the limitations of the native Cortistatin as a therapeutic agent. This study provides an efficient approach to the rational design of Cortistatin analogs and opens up new possibilities for the treatment of patients that fail to respond to other therapies
Topical Administration of Somatostatin Prevents Retinal Neurodegeneration in Experimental Diabetes
No full textβ,γ-Diamino acid: an original building block for hybrid α/γ-peptide synthesis with extra hydrogen bond donating group
No full textRh-Catalyzed Asymmetric Hydrogenation of g-Phthalimido-Substituted a,b-Unsaturated Carboxylic Acid Esters: An Efficient Enantioselective Synthesis of b-Aryl-g-amino Acids
No full textMechanistic aspects of CPP-mediated intracellular drug delivery: Relevance of CPP self-assembly
No full textPositive and negative ion electrospray tandem mass spectrometry (ESI MS/MS) of boc-protected peptides containing repeats of L-Ala-γ 4Caa/γ 4Caa-L-Ala: Differentiation of some positional isomeric peptides
No full textSynthesis and in vitro inhibition properties of oligonucleotide conjugates carrying amphipathic proline-rich peptide derivatives of the sweet arrow peptide (SAP)
No full textRecommended from our members
Enantioselective Intramolecular Michael Addition of Nitronates onto Conjugated Esters: Access to Cyclic γ-Amino Acids with up to Three Stereocenters
No full textA highly stereoselective synthesis of conformationally constrained cyclic γ-amino acids has been devised. The key step involves an intramolecular cyclization of a nitronate onto a conjugated ester, promoted by a bifunctional thiourea catalyst. This methodology has been successfully applied to generate a variety of γ-amino acids, including some containing three contiguous stereocenters, with very high diastereoselectivity and excellent enantioselectivity. It is postulated that an interaction that is key to the success of the process is the simultaneous coordination of the thiourea functionality to both the conjugated ester and the nitronate. Finally, the synthetic utility of these compounds is demonstrated in the synthesis of two dipeptides derived from the C- and N-termini
HIV Fusion Peptide and Its Cross-Linked Oligomers: Efficient Syntheses, Significance of the Trimer in Fusion Activity, Correlation of β Strand Conformation with Membrane Cholesterol, and Proximity to Lipid Headgroups
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