- Design criteria for minimalist mimics of protein-protein interface segments
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Small molecules that can interrupt or inhibit protein-protein interactions (PPIs) are valuable as probes in chemical biology and medicinal chemistry, but they are also notoriously difficult to develop. Design of non-peptidic small molecules that mimic ami
- Taechalertpaisarn, Jaru,Lyu, Rui-Liang,Arancillo, Maritess,Lin, Chen-Ming,Jiang, Zhengyang,Perez, Lisa M.,Ioerger, Thomas R.,Burgess, Kevin
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supporting information
p. 908 - 915
(2019/01/30)
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- MACROCYCLIZATION OF PEPTIDOMIMETICS
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The invention provides an improved method of macrocyclization of peptidomimetics, as measured by isolated yields and product distribution, which comprises substitution of one or more of the backbone amide C=O bonds with a turn-inducing motif. The method is general with enhancements seen across a range of ring sizes (e.g. tri-, tetra-, penta- and hexapeptides). Specifically, the invention provides a peptidomimetic macrocycle comprising a carbonyl bioisosteric turn-inducing element having the structure: (I) wherein X is a heteroatom; and wherein R1 to R6 are each independently selected from alkyl, aryl, heteroaryl and H.
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Page/Page column 36; 41-43
(2019/10/19)
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- Total synthesis and biological evaluation of tamandarin B analogues
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(Chemical Equation Presented) Tamandarins A and B are a class of marine natural cyclodepsipeptides with structures and biological activities closely related to those of the didemnins. The easier synthetic access to tamandarins accelerates the preparation of new macrocyclic derivatives of this family of antitumor, antiviral, and immunosuppressive compounds. The optimization of the previously reported synthetic route to tamandarins by changing the macrolactamization site from Nst1 and Thr6 to Pro 4 and N,O-Me2Tyr5 residues led to a significant improvement in the reaction yield. Using this new synthetic approach, four new macrocyclic analogues of tamandarin B were prepared and evaluated for anticancer activity. These results provide further insight into the structure-activity relationship of the tamandarins and didemnins.
- Adrio, Javier,Cuevas, Carmen,Manzanares, Ignacio,Joullie, Madeleine M.
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p. 5129 - 5138
(2008/02/07)
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- Application of a unique automated synthesis system for solution-phase peptide synthesis
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An automated synthesis system, which is suitable for repetitive syntheses using similar reaction procedures, was used to synthesize systematically a library of all possible dipeptides (25) and tripeptides (125) from 5 protected amino acids. The apparatus has also been applied to the automated synthesis of 10 fragment tripeptide derivatives that are constituents of the hormone PACAP-27. The measured molecular optical rotation values of the library of 125 tripeptides were found to correlate well with calculated values obtained by summation of the molecular optical rotation values for the constituent amino acids.
- Sugawara,Kobayashi,Okamoto,Kitada,Fujino
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p. 1272 - 1280
(2007/10/02)
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- Biodegradable microspheres. 16. Synthesis of primaquine-peptide spacers for lysosomal release from starch microparticles
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Classical procedures of peptide synthesis were applied to synthesize four groups of compounds, and analytical methods were developed for each of them. Two of the groups are tetrapeptide derivatives of the antileishmanial drug primaquine (PQ), with general structure NH2-X-Leu-Ala-Y-PQ. In the first group, Leu, Tyr, Lys, and Asp were used in the Y position, while X was Ala. In the second group, Ala, Tyr, Lys, and Asp were used in the X position, while Y was Leu. The derivatives are intended to be coupled, via their free α-amino group, to polyacryl starch microparticles, lysosomotropic drug carriers developed in our laboratory. Thus, a systematic study of the significance of the varying amino acid composition of the tetrapeptide spacer arm for the rate of lysosomal enzymatic release of PQ can be possible. A third group, composing ε-aminocaproic acid-PQ derivatives which lack a free α-amino group, was synthesized. This was done to study the importance of enzymes, other than aminopeptidases, during lysosomal degradation of these derivatives. To allow HPLC analysis of the pattern of degradation of tetrapeptide-PQ derivatives, some shorter peptide-PQ derivatives (group four) were prepared as well.
- Borissova,Lammek,Stjarnkvist,Sjoholm
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p. 249 - 255
(2007/10/02)
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