Combinatorial Peptide Libraries: Mining for Cell-Binding Peptides

Gray, Bethany Powell; Brown, Kathlynn C.

doi:10.1021/cr400166n

Cited by 193 publications

(204 citation statements)

References 606 publications

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“…Although numerous tumor-targeting peptides have been isolated using in vitro panning against cultured cells, several challenges still remain in this field (16). In particular, experimental approaches for systematic target identification are still lacking (15); this is a key problem, because accurate identification of peptide-targeted molecules is very important for basic and clinical research.…”

Section: Introductionmentioning

confidence: 99%

α-Enolase–binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer

Kuo

Hong

et al. 2015

Sci. Transl. Med.

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Colorectal cancer is one of the most commonly diagnosed cancers and a leading cause of cancer mortality worldwide. Current treatment for colorectal cancer results in only limited success, and more effective therapeutic approaches are thus urgently needed. The development of new methods for early detection and effective treatments for cancer is contingent on the identification of biomarkers on the surface of cancer cells, as well as isolation of tumor-specific ligands with high binding affinity to such biomarkers. In vitro biopanning of a phage-displayed peptide library was used to identify specific peptides binding to human colorectal carcinoma cells. The targeting peptide pHCT74 showed the greatest potential for drug delivery in both in vitro and in vivo studies. The use of biotinylated peptides combined with an affinity trapping method and liquid chromatography-tandem mass spectrometry identified the target protein for the pHCT74 peptide as α-enolase. In animal model studies, combined pHCT74-conjugated liposomal doxorubicin (pHCT74-LD) and pHCT74-conjugated liposomal vinorelbine (pHCT74-sLV) therapy exhibited an enhanced antitumor effect and markedly extended the survival of mice with human colorectal cancer in subcutaneous and orthotopic models. Our findings indicate that α-enolase-targeted lipid nanoparticles have great potential for application in targeted drug delivery systems for colorectal cancer therapy.

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Section: Introductionmentioning

confidence: 99%

α-Enolase–binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer

Kuo

Hong

et al. 2015

Sci. Transl. Med.

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“…However, immunological limitations associated with non-humanized proteins make their application complicated. Short peptides usually do not induce immune response; therefore recently effective selection approaches for peptide binding endothelial receptors have been developed (Powell Gray & Brown 2014). Brain-targeting of nanodrugs using convenient peptide vectors represent excellent nanodrug candidates for the advanced treatment of HIV infection in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Amphiphilic Cationic Nanogels as Brain-Targeted Carriers for Activated Nucleoside Reverse Transcriptase Inhibitors

Warren

Makarov

et al. 2015

J Neuroimmune Pharmacol

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Progress in AIDS treatment shifted emphasis towards limiting adverse effects of antiviral drugs while improving the treatment of hard-to-reach viral reservoirs. Many therapeutic nucleoside reverse transcriptase inhibitors (NRTI) have a limited access to the central nervous system (CNS). Increased NRTI levels induced various complications during the therapy, including neurotoxicity, due to the NRTI toxicity to mitochondria. Here, we describe an innovative design of biodegradable cationic cholesterol-ε-polylysine nanogel carriers for delivery of triphosphorylated NRTIs that demonstrated high anti-HIV activity along with low neurotoxicity, warranting minimal side effects following systemic administration. Efficient CNS targeting was achieved by nanogel modification with brain-specific peptide vectors. Novel dual and triple-drug nanoformulations, analogous to therapeutic NRTI cocktails, displayed equal or higher antiviral activity in HIV-infected macrophages compared to free drugs. Our results suggest potential alternative approach to HIV-1 treatment focused on the effective nanodrug delivery to viral reservoirs in the CNS and reduced neurotoxicity.

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“…[236] Synthetic collections of peptides, meanwhile, can be chemically or biologically derived, with the former based on traditional one-bead-one-compound (OBOC) or positional scanning combinatorial synthesis approaches. [237] In OBOC, a high concentration of a single peptide sequence is displayed on approximately 100 μm beads, generating libraries of 10 6 -10 8 compounds, [238] though the high multivalency on individual beads can lead to selection of low affinity binders to target ligands. In positional scanning synthetic libraries, a single amino acid position is kept constant while other positions are varied and the resultant collections are not bound to supports, allowing solution-based screening for binding.…”

Section: Sources and Synthesis Of Peptidesmentioning

confidence: 99%

Adding Functions to Biomaterial Surfaces through Protein Incorporation

et al. 2016

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The concept of biomaterials has evolved from one of inert mechanical supports with a long-term, biologically inactive role in the body into complex matrices that exhibit selective cell binding, promote proliferation and matrix production, and may ultimately become replaced by newly generated tissues in vivo. Functionalization of material surfaces with biomolecules is critical to their ability to evade immunorecognition, interact productively with surrounding tissues and extracellular matrix, and avoid bacterial colonization. Antibody molecules and their derived fragments are commonly immobilized on materials to mediate coating with specific cell types in fields such as stent endothelialization and drug delivery. The incorporation of growth factors into biomaterials has found application in promoting and accelerating bone formation in osteogenerative and related applications. Peptides and extracellular matrix proteins can impart biomolecule- and cell-specificities to materials while antimicrobial peptides have found roles in preventing biofilm formation on devices and implants. In this progress report, we detail developments in the use of diverse proteins and peptides to modify the surfaces of hard biomaterials in vivo and in vitro. Chemical approaches to immobilizing active biomolecules are presented, as well as platform technologies for isolation or generation of natural or synthetic molecules suitable for biomaterial functionalization.

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Combinatorial Peptide Libraries: Mining for Cell-Binding Peptides

Cited by 193 publications

References 606 publications

α-Enolase–binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer

α-Enolase–binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer

Amphiphilic Cationic Nanogels as Brain-Targeted Carriers for Activated Nucleoside Reverse Transcriptase Inhibitors

Adding Functions to Biomaterial Surfaces through Protein Incorporation

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