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In recognition of the key role played by integrins in several life-threatening dysfunctions, the search for novel small-molecule probes that selectively recognize these surface receptors is still open and widely pursued. Inspired by previously established aminoproline (Amp)-RGD based cyclopeptidomimetics with attracting αVβ3 integrin affinity and selectivity, the design and straightforward synthesis of 18 new AmpRGD chemotypes bearing additional structural variants were herein implemented, to shift toward peptide-like αVβ6 integrin targeted binders. The ligand competence of the synthesized products toward αVβ6 was evaluated in competitive binding assays on isolated receptors, and αVβ6/αVβ3 selectivity was determined for a subgroup of compounds, resulting in the identification of four very promising candidates. SAR considerations and docking simulations allowed us to appreciate the key structural features responsible for the observed activity.

A new GC-MS method was developed for the analysis of ascaulitoxin, its aglycone, and 4-amino-D-proline, which are phytotoxins with potential herbicidal activity produced by Ascochyta caulina. The method involved directly treating the lyophilized culture filtrate with a derivatizing reagent, converting the mixture of toxins in the filtrate to their corresponding trimethylsilyl derivatives, and consequent analysis by EI-MS. The method is rapid, sensitive and highly specific for the identification and analysis of the toxins in a complex sample matrix. Analysis of culture filtrates using this method suggested that phytotoxicity correlates with the level of ascaulitoxin in the culture filtrate. A new method for the purification of 2,4,7-triamino-5-hydroxyoctandioic acid, the aglycone of ascaulitoxin, is also described.

Stereospecific syntheses of (2 S ,3 R ) 3-carboxyproline and (2 S ,3 R ) 3-aminoproline are reported which make use of the stereospecific alkylation of (4 S )- N -( t -butyldimethylsilyl)azetidin-2-one 4-carboxylic acid with the cyclic sulfate derived from ethylene glycol.

4S-Aminoproline polypeptide 2 forms unusual β-structure in trifluoroethanol that switches to the polyproline II (PPII) form in aqueous medium, while 4R-aminoproline peptide 1 retains PPII form in both solvents. This first instance of a polyproline derivative showing a β-structure is attributed to competitive pH-dependent (4-NH(3)(+)/NH(2)) stereoelectronic effect (4R vs 4S) and the overriding importance of stereospecific intra/intermolecular H-bonding in (2,4)-cis-4S-aminoproline in contrast to (2,4)-trans-4R-aminoproline oligomers.

[structure: see text] (2R,3R)-Aminoproline, a pyrrolidine-based beta-amino acid, was synthesized and incorporated into hexa-beta-peptide 4. This residue confers water solubility when the ring nitrogen is protonated and allows for 12-helix formation in aqueous solution. Circular dichroism spectra display the 12-helical signature, and 12-helical structure was confirmed by 2D NMR analysis.

4R/S-Aminoprolines when present in the X-position of collagen peptide [pro(X)-pro(Y)-Gly]n exhibit pH- and stereochemistry-dependent effects on triplex stability.

1-Aminoproline-U-14C was administered to rats by intraperitoneal injection. The radioactivity was distributed in all the tissues examined. Among them, kidney, lung, liver and spleen had high specific activity. The radioactivity in the tissues and blood decreased rapidly as a function of time, except in brain. About 80% of the radioactivity administered was excreted in urine within 24 hr. Besides intact 1-aminoproline, several radioactive compounds were detected in the urine sample, and one of them was identified as 1-aminopropyl hydrazone of pyridoxal.

By the intraperitoneal injection of 1-aminoproline and l -[U- 14 C]methionine, three unidentified radioactive compounds appeared abnormally in rat urine together with large amounts of radioactive l -cystathionine. One of them was identified as S -[ l -2-(acetylamino)-2-carboxyethyl]- l -homocysteine and the other two compounds were proved to be the diastereoisomers of l -cystathionine sulfoxide. These observations indicate that the disturbance of methionine metabolism by 1-aminoproline resulted in the accumulation of l -cystathionine and its novel derivatives.