Synthesis and conformational study of two L‐prolyl‐L‐leucyl‐glycinamide analogues with a reduced peptide bond

Elst, P. Vander; Elseviers, M.; Cock, E. De; Marsenille, M. Van; Tourwé, Dirk; Binst, G. Van

doi:10.1111/j.1399-3011.1986.tb01059.x

Cited by 17 publications

(1 citation statement)

References 21 publications

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“…Clinical assays demonstrated that MIF-1, alone, has the potential to alleviate the motor symptoms of PD, , to potentiate the effect of levodopa when used in a cotherapy regimen, and to reduce the levodopa-induced dyskinesia . Despite its great potential, pharmacokinetic issues associated with this neuropeptide (e.g., low gastrointestinal absorption and lability toward CNS proteases) hinder the progression of clinical assays and its use in PD. − Over the years, several strategies have been employed to improve the stability and activity of MIF-1, including the development of peptidomimetics, − and chemical conjugation with a sinapic acid at the N -terminal and biogenic amines as spacers at the C -terminal position …”

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confidence: 99%

Stapling Amantadine to Melanostatin Neuropeptide: Discovery of Potent Positive Allosteric Modulators of the D₂ Receptors

Silva-Reis,

Correia,

Costa-Almeida

et al. 2023

ACS Med. Chem. Lett.

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This work describes the synthesis and pharmacological and toxicological evaluation of melanostatin (MIF-1) bioconjugates with amantadine (Am) via a peptide linkage. The data from the functional assays at human dopamine D2 receptors (hD2R) showed that bioconjugates 1 (EC50 = 26.39 ± 3.37 nM) and 2 (EC50 = 17.82 ± 4.24 nM) promote a 3.3- and 4.9-fold increase of dopamine potency, respectively, at 0.01 nM, with no effect on the efficacy (E max = 100%). In this assay, MIF-1 was only active at the highest concentration tested (EC50 = 23.64 ± 6.73 nM, at 1 nM). Cytotoxicity assays in differentiated SH-SY5Y cells showed that both MIF-1 (94.09 ± 5.75%, p < 0.05) and carbamate derivative 2 (89.73 ± 4.95%, p < 0.0001) exhibited mild but statistical significant toxicity (assessed through the MTT reduction assay) at 200 μM, while conjugate 1 was found nontoxic at this concentration.

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confidence: 99%

Stapling Amantadine to Melanostatin Neuropeptide: Discovery of Potent Positive Allosteric Modulators of the D₂ Receptors

Silva-Reis,

Correia,

Costa-Almeida

et al. 2023

ACS Med. Chem. Lett.

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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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Pseudopeptides and β folding: X‐ray structures compared with structures in solution

Aubry

Marraud

1989

Biopolymers

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In order to restrain the flexibility of the peptide molecules and reduce their biodegradation, modifications of the main chain are now introduced in pseudopeptide analogues. Surprisingly, there is very little data on the conformational properties of these derivatives. We have examined pseudopeptide analogues of RCO-X-Y-NHR' model dipeptides in the depsi, N-methylated, reduced, retro, alpha, beta-dehydro, beta-amino acid, and hydrazino series, in the solid state by x-ray diffraction, and in solution by ir and 1H-nmr spectroscopy. This study provides us with accurate dimensions of the peptide surrogates, and gives some information on the conformational tendencies induced by these substitutions, with reference to those of the related dipeptide sequences.

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Synthesis and conformational study of two L‐prolyl‐L‐leucyl‐glycinamide analogues with a reduced peptide bond

Cited by 17 publications

References 21 publications

Stapling Amantadine to Melanostatin Neuropeptide: Discovery of Potent Positive Allosteric Modulators of the D₂ Receptors

Stapling Amantadine to Melanostatin Neuropeptide: Discovery of Potent Positive Allosteric Modulators of the D₂ Receptors

Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents

Pseudopeptides and β folding: X‐ray structures compared with structures in solution

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Synthesis and conformational study of two L‐prolyl‐L‐leucyl‐glycinamide analogues with a reduced peptide bond

Cited by 17 publications

References 21 publications

Stapling Amantadine to Melanostatin Neuropeptide: Discovery of Potent Positive Allosteric Modulators of the D2 Receptors

Stapling Amantadine to Melanostatin Neuropeptide: Discovery of Potent Positive Allosteric Modulators of the D2 Receptors

Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents

Pseudopeptides and β folding: X‐ray structures compared with structures in solution

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Stapling Amantadine to Melanostatin Neuropeptide: Discovery of Potent Positive Allosteric Modulators of the D₂ Receptors

Stapling Amantadine to Melanostatin Neuropeptide: Discovery of Potent Positive Allosteric Modulators of the D₂ Receptors