Development of peptidomimetic ligands of Pro-Leu-Gly-NH₂ as allosteric modulators of the dopamine D₂ receptor

• Swapna Bhagwanth,
• Ram K. Mishra and
• Rodney L. Johnson

Beilstein J. Org. Chem. 2013, 9, 204–214, doi:10.3762/bjoc.9.24

• /bjoc.9.24 Abstract A variety of stable, small-molecule peptidomimetic ligands have been developed to elucidate the mechanism by which the neuropeptide Pro-Leu-Gly-NH2 (PLG) modulates dopaminergic neurotransmission. Photoaffinity labeling ligands based upon PLG peptidomimetics have been used to

• changes in the spiro-bicyclic dopamine receptor modulators are capable of causing major changes in the modulatory activity of PLG peptidomimetics. Keywords: allosteric modulation; dopamine D2 receptor; peptidomimetic; Pro-Leu-Gly-NH2; spiro-bicyclic scaffold; Review There has been an increasing effort

• Parkinson’s disease and tardive dyskinesia, the peptide nature of PLG limits its potential as a drug [10][11]. Thus, efforts were initiated to design peptidomimetic analogues of PLG in the hope of developing agents that would possess the same activity as PLG, but have better pharmacokinetic properties. As

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• , piazza Leonardo da Vinci 32, 20132 Milano, Italy 10.3762/bjoc.9.17 Abstract Aiming at restricting the conformational freedom of tryptophan-containing peptide ligands, we designed a THBC (tetrahydro-β-carboline)-DKP (diketopiperazine)-based peptidomimetic scaffold capable of arranging in an unusual α

• attention in recent years because of their broad biological activities [11][12] and therapeutic applications, ranging from antibiotics [13] to anticancer agents [14]. Moreover, the DKP moiety has been exploited as a peptidomimetic scaffold [15][16][17]. Structural unification of THBC and DKP pharmacophores

• of pharmacophore-based combinatorial libraries [26] and identification of new peptidomimetic scaffolds of potential interest in drug discovery [27][28][29][30], we evaluated the THBC-DKP-based scaffold as a potential suitable motif for the creation of unusual reverse-turn nucleators. Reverse turns

Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics

• Workalemahu M. Berhanu,
• Mohamed A. Ibrahim,
• Girinath G. Pillai,
• Alexander A. Oliferenko,
• Levan Khelashvili,
• Farukh Jabeen,
• Bushra Mirza,
• Farzana Latif Ansari,
• Ihsan ul-Haq,
• Said A. El-Feky and
• Alan R. Katritzky

Beilstein J. Org. Chem. 2012, 8, 1146–1160, doi:10.3762/bjoc.8.128

• studied in order to identify new promising cyclic scaffolds. A large descriptor space coupled with cluster analysis was employed to digitize known antibacterial structures and to gauge the potential of new peptidomimetic macrocycles, which were conveniently synthesized by acylbenzotriazole methodology

• consistent analysis and comparison, the principles of molecular similarity have never been used in the design of peptides. The aim of the present work is thus three-fold: (i) To identify promising peptidomimetic scaffolds by using molecular similarity; (ii) to design a range of cyclic pyridine-containing

• -, O-, C- and S-acylations. Results and Discussion Similarity analysis Our literature search identified the thirty three cyclic peptides and peptidomimetic structures given in Table 1. All the minimum inhibition constants (MIC) are pertinent to Staphylococcus aureus. These include (i) one 12-membered

Multicomponent synthesis of artificial nucleases and their RNase and DNase activity

• Anton V. Gulevich,
• Lyudmila S. Koroleva,
• Olga V. Morozova,
• Valentina N. Bakhvalova,
• Vladimir N. Silnikov and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2011, 7, 1135–1140, doi:10.3762/bjoc.7.131

• activity of the new compounds towards single-stranded RNA and double-stranded circular DNA. Keywords: DNA; isocyanide; multicomponent reaction; organocatalysis; peptidomimetic; RNA; Introduction RNA cleavage can serve as a molecular tool for biological research [1], as well as for development of

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring

• Arumugam Kodimuthali,
• Padala Lakshmi Prasunamba and
• Manojit Pal

Beilstein J. Org. Chem. 2010, 6, No. 71, doi:10.3762/bjoc.6.71

• currently being evaluated in phase 3 clinical trials [8][9][10]. This compound was identified by replacing the quinazolinone moiety of another inhibitor B with a pyrimidine dione (Figure 1) [8]. All these inhibitors that belong to the non-peptidomimetic class contain an aminopiperidinyl moiety which

Synthesis of methylenebisamides using CC- or DCMT- activated DMSO

• Qiang Wang,
• Lili Sun,
• Yu Jiang and
• Chunbao Li

Beilstein J. Org. Chem. 2008, 4, No. 51, doi:10.3762/bjoc.4.51

• 315211, China. 10.3762/bjoc.4.51 Abstract Bisamides are key fragments for the introduction of gem-diaminoalkyl residues into retroinverso pseudopeptide derivatives and in the synthesis of peptidomimetic compounds. The literature methods for these types of compounds have certain drawbacks. In particular

• reaction of nucleophilic reagents such as amides, alcohols, and phenols with DMSO activated by CC. The amide moiety is an important constituent of many biologically significant compounds. Bisamides are of considerable interest in the synthesis of peptidomimetic compounds [15]. In particular, bisamides are

Synthesis of new triazole- based trifluoromethyl scaffolds

• Michela Martinelli,
• Thierry Milcent,
• Sandrine Ongeri and
• Benoit Crousse

Beilstein J. Org. Chem. 2008, 4, No. 19, doi:10.3762/bjoc.4.19

• ][17]. Furthermore, the development of CF3-containing scaffolds has gained a real interest especially in the peptidomimetic area [18][19][20][21]. In continuation of our interest in the synthesis of original trifluoromethyl compounds [22][23][24][25][26], and in order to study the influence of

One-pot synthesis of novel 1H-pyrimido[4,5-c][1,2]diazepines and pyrazolo[3,4-d]pyrimidines

• Dipak Prajapati,
• Partha P. Baruah,
• Baikuntha J. Gogoi and
• Jagir S. Sandhu

Beilstein J. Org. Chem. 2006, 2, No. 5, doi:10.1186/1860-5397-2-5

• minor tranquiliser, a large number of seven-membered heterocyclic compounds with the benzodiazepine moiety have been synthesized and tested for psychotropic properties.[29] This moiety has been found to represent a versatile template in peptidomimetic design and it is also found in several other