Synthesis and Biological Activities of Bradykinin Analogues with Ψ(E,CH=CH) and Ψ(CH<sub>2</sub>‐NH) Isosteric Peptide Bond Replacements

Scarso, Alessandro; Degelaen, J.; Viville, R.; Cock, E. De; Marsenille, M. Van; Auwera, L. Van Der; Tourwé, Dirk; Binst, G. Van

doi:10.1002/bscb.19911000506

Cited by 13 publications

(1 citation statement)

References 18 publications

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“…To avoid the specific nucleophilic attack of enzymes toward the amide bond, Tourwé et al replaced the R-CO-NH-R´ motif by different isosteres consisting of a set of atoms that can mimic the sterical and/or electronical properties of the peptide [9][10][11]. All these features are desirable in peptide alike drugs such that they can remain stable longer in the human body [12,13].…”

Section: Introductionmentioning

confidence: 99%

Quantum similarity of isosteres coordinate versus momentum space and influence of alignment

Vivas‐Reyes

Arias

Vandenbussche

et al. 2010

Journal of Molecular Structure: THEOCHEM

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To refer to or to cite this work, please use the citation to the published version:Vivas-Reyes, R.; Ariasa, A.; Vandenbussche, J.; Bultinck, P.; Van Alsenoy, C. ABSTRACTMolecular quantum similarity was studied for a set of peptide isosteres analyzed before by Boon et al.(Chemical Physics Letters, 1998, 295 122). Overlap and Coulomb similarity measures in coordinate space were calculated using the TGSA (Topo-Geometrical Superposition Algorithm) algorithm for the alignment of molecules instead of the one used in the previous work, and a comparison between the superposition methods was made. Overlap and first order moment similarity indices in momentum space are computed for the same alignment. The results illustrate the importance of the alignment algorithm for the evaluation of molecular similarity in a given set of molecules and show that the degree of similarity depends dramatically on the similarity measure used and the space in which the similarity is computed. For a small set of propane derivatives where the similarity ranking is known from drug design, only momentum space similarity integrals give the expected similarity ordering.2

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Section: Introductionmentioning

confidence: 99%

Quantum similarity of isosteres coordinate versus momentum space and influence of alignment

Vivas‐Reyes

Arias

Vandenbussche

et al. 2010

Journal of Molecular Structure: THEOCHEM

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Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents

2002

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Reductive amination is an important tool for synthetic organic chemists in the construction of carbon‐nitrogen bonds. This reaction, also termed reductive alkylation, involves condensation of an aldehyde or ketone with an amine in the presence of a reducing agent. A wide variety of substrates can be used including aliphatic and aromatic aldehydes and ketones, and even benzophenones. A range of amines from ammonia to aromatic amines, including those with electron‐withdrawing substituents, can be employed. For particularly sluggish reactions, such as those involving weakly electrophilic carbonyl groups, poorly nucleophilic amines, or sterically congested reactive centers, additives such as molecular sieves or Lewis acids are often useful. This chapter focuses on those conditions in which the carbonyl component, amine, and reducing reagent react in the same vessel. This review is restricted to reductive aminations using borohydride and borane reducing agents. This chapter concentrates on reductive amination chemistry mediated by borohydride and other boron‐containing reducing agents from 1971, the year when sodium cyanoborohydride was introduced, through the middle of 1999. In addition to reductive aminations of aldehyde and ketone substrates, reactions of related structures including acetals, aminals, ketals, carboxylic acids, nitriles, and dicarbonyls that form a nitrogen‐containing ring are reviewed. Intramolecular processes in which the substrate contains both the carbonyl and amine moieties are described. The intramolecular variant is a useful method for preparing cyclic amines. All of the various boron‐containing hydride sources in reductive aminations, including labeled metal hydrides, are reviewed. Instances of reductive aminations that failed are described. Applications of this method to a solid support in parallel synthesis in combinatorial chemistry as well as reductive aminations that proceed in tandem with a second reaction such as reductive lactamizations are discussed.

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Morphiceptin and β‐casomorphin‐5 analogues containing a reduced peptide bond: Selective μ‐receptor agonists and a novel μ antagonist, H‐Tyr‐Proψ(CH₂‐NH)Phe‐Pro‐Gly‐OH

et al. 1992

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In order to prevent enzymatic degradation of beta-casomorphin-5 (1) and morphiceptin, reduced peptide bonds were incorporated at the 2-3 and 3-4 bonds, respectively. The analogues were synthesized by a combination of solid phase methodology and reductive alkylation of resin-bound peptide amines with Boc-amino acid aldehydes (Boc: tert-butyloxycarbonyl) in the presence of NaBH3CN. During reversed phase high pressure liquid chromatography purification, peak shape distortions could be observed. Epimerization was excluded, based on gas chromatography/mass spectroscopy analysis, which indicated acceptable levels of racemization (less than 3%) in the crude product. Instead, the phenomena could be attributed to slow cis/trans isomerizations originating from the Xxx-Pro bonds in the sequence. The presence of different conformational isomers was also established by 1H-nmr spectroscopy in DMSO-d6. All analogues showed high stability in blood plasma, enhanced binding affinity for the mu receptor, and very low binding to the delta receptor. While the Phe 3 psi(CH2-N)Pro4 analogues (3) and (5) displayed agonist activity, the Pro 2 psi(CH2-NH)Phe3 modified analogue (2) showed antagonist activity comparable to D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2.

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Synthesis and Biological Activities of Bradykinin Analogues with Ψ(E,CH=CH) and Ψ(CH₂‐NH) Isosteric Peptide Bond Replacements

Cited by 13 publications

References 18 publications

Quantum similarity of isosteres coordinate versus momentum space and influence of alignment

Quantum similarity of isosteres coordinate versus momentum space and influence of alignment

Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents

Morphiceptin and β‐casomorphin‐5 analogues containing a reduced peptide bond: Selective μ‐receptor agonists and a novel μ antagonist, H‐Tyr‐Proψ(CH₂‐NH)Phe‐Pro‐Gly‐OH

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Synthesis and Biological Activities of Bradykinin Analogues with Ψ(E,CH=CH) and Ψ(CH2‐NH) Isosteric Peptide Bond Replacements

Cited by 13 publications

References 18 publications

Quantum similarity of isosteres coordinate versus momentum space and influence of alignment

Quantum similarity of isosteres coordinate versus momentum space and influence of alignment

Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents

Morphiceptin and β‐casomorphin‐5 analogues containing a reduced peptide bond: Selective μ‐receptor agonists and a novel μ antagonist, H‐Tyr‐Proψ(CH2‐NH)Phe‐Pro‐Gly‐OH

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Synthesis and Biological Activities of Bradykinin Analogues with Ψ(E,CH=CH) and Ψ(CH₂‐NH) Isosteric Peptide Bond Replacements

Morphiceptin and β‐casomorphin‐5 analogues containing a reduced peptide bond: Selective μ‐receptor agonists and a novel μ antagonist, H‐Tyr‐Proψ(CH₂‐NH)Phe‐Pro‐Gly‐OH