Tripeptide Motifs in Biology: Targets for Peptidomimetic Design

Ung, Phuc; Winkler, David A.

doi:10.1021/jm1012984

Cited by 73 publications

(56 citation statements)

References 151 publications

(217 reference statements)

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“…Among the peptide family, short peptides are very appealing for drug discovery and development because of their cost-effectiveness, possibility of oral administration, and simplicity to perform molecular structural and quantitative structure-activity studies [1]. Small peptides are under development as possible antitumour agents as well.…”

Section: Introductionmentioning

confidence: 99%

In vitro assessment of the cytotoxic effects of novel RGD analogues

Balacheva¹,

Илиев²,

Detcheva³

et al. 2012

Biodiscovery

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The RGD sequence is present in many extracellular matrix proteins and intracellular proteins, including caspases. Synthetic RGD peptides may affect adhesion, migration and tumour metastasis, or directly induce apoptosis. Several RGD peptides were synthesized, and their anti-adhesive and cytotoxic properties were analyzed in vitro.Here we present the cytotoxic activities of RGD, R(NO 2 )GD, CavGD and RGD-OMe on non-tumour 3T3 cells and tumour cell lines HepG2 and MCF-7. The cell growth inhibitory effects of RGD-OMe are significantly higher than those of RGD on the cell lines used. Evidently the modification in the carboxylic group of RGD with simple esterification increases the cell growth inhibitory effects of the parent compound.

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Section: Introductionmentioning

confidence: 99%

In vitro assessment of the cytotoxic effects of novel RGD analogues

Balacheva¹,

Илиев²,

Detcheva³

et al. 2012

Biodiscovery

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“…These methods have been used to design and optimise green pesticides [16][17][18][19][20] in collaboration with Du Pont and Schering Plough, have discovered new peptides and small molecules to control stem cells and cancers, [21][22][23][24][25][26][27] are accelerating the development of biomaterials for implantation and stem cell culture, [28][29][30][31][32][33] have provided new scientific insight into the potential adverse properties of nanomaterials, [34][35][36][37][38] have yielded clinical candidates for Australian SMEs and international companies, and were instrumental in the discovery of antibiotics [39,40] with a novel mode of action for the biotechnology spin off company, Betabiotics. Some of this research is discussed in more detail in the following sections.…”

Section: The Threat and Promise Of The Vastness Of Chemical Spacementioning

confidence: 99%

“…We reviewed the literature and established that this minimal information unit may be a tripeptide motif. [39] Some tripeptides have been mimicked by small molecules, while many more potentially important motifs have yet to be discovered and used for drug design. The idea that three contiguous amino acids is biologically important is consistent with Reynolds et al and Neduva and Russell's suggestion that 25 heavy atoms (the average number in a tripeptide) provides optimal ligand affinity.…”

Section: Self-assembling Amphiphilic Drug Delivery Systemsmentioning

confidence: 99%

Adrien Albert Award: How to Mine Chemistry Space for New Drugs and Biomedical Therapies

Winkler

2015

Aust. J. Chem.

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It is clear that the sizes of chemical, 'drug-like', and materials spaces are enormous. If scientists working in established therapeutic, and newly established regenerative medicine fields are to discover better molecules or materials, they must find better ways of probing these enormous spaces. There are essentially five ways that this can be achieved: combinatorial and high throughput synthesis and screening approaches; fragment-based methods; de novo molecular design, design of experiments, diversity libraries; supramolecular approaches; evolutionary approaches. These methods either synthesise materials and screen them more quickly, or constrain chemical spaces using biology or other types of 'fitness functions'. High throughput experimental approaches cannot explore more than a minute part of chemical space. We are nevertheless entering into an era that is data dominated. High throughput experiments, robotics, automated crystallographic beam lines, combinatorial and flow synthesis, high content screening, and the 'omics' technologies are providing a flood of data, and efficient methods for extracting meaning from it are essential. This paper describes how new developments in mathematics have provided excellent, robust computational modelling tools for exploring large chemical spaces, for extracting meaning from large datasets, for designing new bioactive agents and materials, and for making truly predictive, quantitative models of the properties of molecules and materials for use in therapeutic and regenerative medicine. We describe these broadly applicable modelling tools and provide examples of their application to serum free stem cell culture, pathogen resistant polymers for implantable devices, new markers and biological mechanisms derived from mathematical analyses of gene array data, and pharmacokinetically important physicochemical properties of small molecules. We also discuss biologically conserved peptide motifs as a design framework for small molecule drugs and give examples of the application of this concept to drug design.

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“…In order to avoid the problems associated with the use of biologically derived whole proteins, some bioactive peptide sequences from oligopeptides have been utilised to engineer SAP scaffolds, such as LAIKNDNLVYVY to shorter motifs such as IKVAV, and RGD [42]. Indeed, tripeptide motifs represent an important class of biological signals, both in structure induction and functionality [43]. As such, these are an ideal target for inclusion within self-assembled scaffolds, both as a SAP and bioactive signal.…”

Section: Functionalisation Of Peptide Materialsmentioning

confidence: 99%

Self-Assembled Peptides: Characterisation and In Vivo Response

Nisbet

Williams

2012

Biointerphases

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The fabrication of tissue engineering scaffolds is a well-established field that has gained recent prominence for the in vivo repair of a variety of tissue types. Recently, increasing levels of sophistication have been engineered into adjuvant scaffolds facilitating the concomitant presentation of a variety of stimuli (both physical and biochemical) to create a range of favourable cellular microenvironments. It is here that self-assembling peptide scaffolds have shown considerable promise as functional biomaterials, as they are not only formed from peptides that are physiologically relevant, but through molecular recognition can offer synergy between the presentation of biochemical and physio-chemical cues. This is achieved through the utilisation of a unique, highly ordered, nano- to microscale 3-D morphology to deliver mechanical and topographical properties to improve, augment or replace physiological function. Here, we will review the structures and forces underpinning the formation of self-assembling scaffolds, and their application in vivo for a variety of tissue types.

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Tripeptide Motifs in Biology: Targets for Peptidomimetic Design

Cited by 73 publications

References 151 publications

In vitro assessment of the cytotoxic effects of novel RGD analogues

In vitro assessment of the cytotoxic effects of novel RGD analogues

Adrien Albert Award: How to Mine Chemistry Space for New Drugs and Biomedical Therapies

Self-Assembled Peptides: Characterisation and In Vivo Response

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