Modified di- and tripeptides of the C-terminal portion of oxytocin and vasopressin as possible cognition activation agents

Abstract

A number of peptides and modified peptides were synthesized and studied for their ability to reverse electroconvulsive shock-induced amnesia in rodents. A few of these peptides were selected for secondary evaluation in tests of short-term memory in rats and aged rhesus monkeys. A number of the peptides and modified peptides were active in the amnesia reversal test. In selected secondary tests, however, the chosen compounds failed to show significant activity in enhancing memory. New methods for preparing methyleneamino and methyleneoxy isosteres of peptides are reported. Other modified peptides also included methylenethio, methylenesulfonyl, and ethylene isosteres in place of the normal peptide amide bond.

Electrochemical and Photophysical Properties of Ruthenium(II) Bipyridyl Complexes with Pendant Alkanethiol Chains in Solution and Anchored to Metal Surfaces

“…1) [52]. The thioacetate was then deprotected to yield the free thiol by adding hydrazine [53] just before the measurements. All details concerning the synthesis and the characterization are reported in the experimental section.…”

Convergent Synthesis of Thioether Containing Peptides

“…In order to examine this parameter, we planned the fragment condensation of thiol-peptides to chloroacylated peptides. As an example we synthesized the somatostatin analogue (6)(7)(8)(9)(10)(11)(12)(13)(14) where Cys14 was replaced by cysteamine (Cys a ; 2-aminoethanethiol) 27. In this experiment, the thiol-peptide 27 contains the acid sensitive Ser(Trt) (O-Trt is cleaved by 1% TFA) and for this reason it was synthesized on Trt-resin 19.…”

“…Among the several peptide modifications, isosteric replacement of a peptide bond represents a viable approach in the rational design of peptidomimetics. Peptidomimetics in which the peptide amide bond is replaced by ethylene (1a)-, methyleneimino (1b)-, methyleneoxy (1c)-and methylenethio (1d)-groups ( Figure 1) were found to exhibit potential pharmaceutical application [4][5][6][7][8][9][10][11][12][13][14][15]. Such modifications alter the physical and chemical properties of the native peptide, reducing its peptide character and leading to peptide analogues with increased resistance to proteolytic enzymes, flexibility and lipophilicity, while they also confer diverse electrostatic properties and new secondary conformations on the peptidomimetic chain, often resulting in improved pharmacokinetic properties [2,16,17].…”

A Library of Conformationally Restricted Saturated Heterocyclic Sulfonyl Chlorides

“…For spectral and physical data, see Rosenberg et al 20 Benzyl 2-[(Acetylthio)methyl]pyrrolidine-1-carboxylate (4d) 21 Yield: 264 g (90%); yellowish oil. 195.2 and 194.8, 154.8, 136.8 and 136.9, 128.5, 128.0, 127.9 and 127.8, 67.0 and 66.7, 56.6 and 57.4, 47.2 and 46.9, 32.3 and 31.4, 30.5, 30.2 and 29.2, 23.7 and 22.9. Anal.…”