141743-15-9Relevant articles and documents
Peptide/peptoid hybrid oligomers: The influence of hydrophobicity and relative side-chain length on antibacterial activity and cell selectivity
Frederiksen, Nicki,Hansen, Paul R.,Bj?rkling, Fredrik,Franzyk, Henrik
, (2019/12/26)
Previous optimisation studies of peptide/peptoid hybrids typically comprise comparison of structurally related analogues displaying different oligomer length and diverse side chains. The present work concerns a systematically constructed series of 16 closely related 12-mer oligomers with an alternating cationic/hydrophobic design, representing a wide range of hydrophobicity and differences in relative side-chain lengths. The aim was to explore and rationalise the structure-activity relationships within a subclass of oligomers displaying variation of three structural features: (i) cationic side-chain length, (ii) hydrophobic side-chain length, and (iii) type of residue that is of a flexible peptoid nature. Increased side-chain length of cationic residues led to reduced hydrophobicity till the side chains became more extended than the aromatic/hydrophobic side chains, at which point hydrophobicity increased slightly. Evaluation of antibacterial activity revealed that analogues with lowest hydrophobicity exhibited reduced activity against E. coli, while oligomers with the shortest cationic side chains were most potent against P. aeruginosa. Thus, membrane-disruptive interaction with P. aeruginosa appears to be promoted by a hydrophobic surface of the oligomers (comprised of the aromatic groups shielding the cationic side chains). Peptidomimetics with short cationic side chains exhibit increased hemolytic properties as well as give rise to decreased HepG2 (hepatoblastoma G2 cell line) cell viability. An optimal hydrophobicity window could be defined by a threshold of minimal hydrophobicity conferring activity toward E. coli and a threshold for maximal hydrophobicity, beyond which cell selectivity was lost.
Apoptotic compounds
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, (2008/06/13)
The invention provides methods and compositions for enhancing apoptosis of pathogenic cells. The general method comprises the of contacting the cells with an effective amount of an AV peptoid, wherein the AV peptoid is a peptide comprising AX1, wherein X1is V, I or L, or a peptide mimetic thereof, which interacts with an Inhibitor of Apoptosis protein (IAP) as measured by IAP binding, procaspase-3 activation or promotion of apoptosis, wherein apoptosis of the pathogenic cells is enhanced. The subject compositions encompass pharmaceutical compositions comprising a therapeutically effective amount of a subject AV peptoid in dosage form and a pharmaceutically acceptable carrier, wherein the AV peptoid is a peptide comprising AX1, wherein X1is V, I or L, or a peptide mimetic thereof, which inhibits the activity of an Inhibitor of Apoptosis protein (IAP) as measured by IAP binding, procaspase-3 activation or promotion of apoptosis. The invention also provides assays for identifying agents which modulates the interaction of an AV peptoid with an IAP, active compounds identified in such screens and their use in the foregoing compositions and therapeutic methods.
Convergent strategies for the attachment of fluorescing reporter groups to peptide nucleic acids in solution and on solid phase
Seitz, Oliver,Koehler, Olaf
, p. 3911 - 3925 (2007/10/03)
The site-selective conjugation of peptide nucleic acids (PNA) with fluorescent reporter groups is essential for the construction of hybridisation probes that can report the presence of a particular DNA sequence. This paper describes convergent methods for
Modified peptide and peptide libraries with protease resistance, derivatives thereof and methods of producing and screening such
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, (2008/06/13)
Peptoids are provided which are polymers comprised of monomer units wherein the monomer units include at least some substitute amino acids and may include conventional amino acids. The peptoids can be synthesized in large numbers so as to provide libraries of peptoids which can be screened in order to isolate peptoids of desired biological activity. Although the peptoids may include amino acids, they preferably include only substituted amino acids and are designed in a manner so as to have a particular biological activity. Certain peptoids are designed to mimic as closely as possible the activity of known proteins. Other peptoids are designed so as to have greater or lesser activity than known proteins and may be designed so as to block known receptor sites and/or elicit a desired immunogenic response and thereby act as vaccines. In that the peptoids are comprised of substitute amino acids they can be designed to have structures which natural proteins cannot conform to. A range of different amino acid substitutes are disclosed, as are their methods of synthesis and methods of using such amino acid substitutes in the synthesis of peptoids and peptoid libraries. Methods of screening the libraries in order to obtain desired peptoids of a particular biological activity are also disclosed. The peptoids are preferably linked to a pharmaceutically active drug forming a conjugate with increased binding affinity to a particular biological receptor site.
Liquid-phase synthesis of polyamide nucleic acids (PNA)
Di Giorgio, Christophe,Pairot, Sandrine,Schwergold, Caroline,Patino, Nadia,Condom, Roger,Farese-Di Giorgio, Audrey,Guedj, Roger
, p. 1937 - 1958 (2007/10/03)
Three liquid-phase processes for the elaboration of short orthogonally protected PNA have been devised. Two of these methods are similar to the convergent and divergent approaches in peptide synthesis. The third process consists in building a fully protected polyamide backbone, by using as many different and orthogonal protecting groups as there are different types of nucleic bases in the targeted polyPNA. Simultaneous and selective cleavage of one kind of protecting group allows the simultaneous attachment of several identical nucleobase units.
Peptoid mixtures
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, (2008/06/13)
Mixtures of peptoids are provided. The subject peptoid mixtures comprise at least five non-homopolymeric polymers of differing sequences having a selected number of monomer units. The polymers of the subject mixtures are preferably selected from the group of compounds of the general formula: Xa --(NR--CH2 --CO)n --Xb, Xa --(O--CHR--CO)n --Xb, Xa --(NH--CHR--CS)n --Xb, Xa --(NOH--CHR--CO)n --Xb, Xa --(O--CHR--CH2 --CO)n --Xb, Xa --(NH--CHR--CH2 --SO2)n --Xb, Xa--(NR--CH2 CH2 --SO2)n --Xb, Xa --(NR--CH2 CH2 --NHCO)n --Xb and Xa --(NR--CH2 CH2 --OCO)n Xb, where each R is independently a side chain capable of interaction with a protein, carbohydrate, lipid or nucleic acid; n is an integer from 2 to 50, inclusive; and Xa and Xb are each independently H, lower alkyl, lower aryl, aralkyl, lower acyl, a polypeptide of 1-100 amino acids, or an effector molecule capable of exhibiting biological activity.
Building Units for N-Backbone Cyclic Peptides. 3. Synthesis of Protected Nα-(ω-Aminoalkyl)amino Acids and Nα-(ω-Carboxyalkyl)amino Acids
Muller, Dan,Zeltser, Irena,Bitan, Gal,Gilon, Chaim
, p. 411 - 416 (2007/10/03)
An improved synthesis of a family of amino acids that contain ω-aminoalkyl groups and of a new family containing ω-carboxyalkyl groups linked to the α-amine is described. The synthesis was performed by alkylation of suitably monoprotected alkylenediamines and protected ω-amino acids with triflates of α-hydroxy acid esters. The reaction proceeded with inversion of configuration yielding optically pure products. The Nα-(ω-aminoalkyl)amino acids and Nα-(ω-carboxyalkyl)amino acids were orthogonally protected to allow their incorporation into peptides by solid-phase peptide synthesis (SPPS) methodology.
Substituted amino compounds, their preparation and their use as inhibitors of thrombocyte-aggregation
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, (2008/06/13)
The present invention relates to novel substituted amino compounds of the formula I: as defined in the present application, and to a process for preparing such compounds. The invention also includes pharmaceutical compositions containing the present c
