Random peptide libraries for target definition

P. Monaci, F. Bartoli, G. Di Zenzo, M. Nuzzo, L. Urbanelli

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Several reports have shown that panning a random peptide library on a purified cellular receptor identified novel ligands for the target molecule. Many novel ligands for integrins, a class of trans-membrane glycoproteins involved in cell migration and tumor invasion, have been identified in this way. Peptides binding to integrins contained the RGD recognition motif flanked by residues which determine their specificity for differing integrins. Such peptides have been successfully used for targeting various gene and drug delivery vehicles to cell expressing the target integrin. When the target receptor needed to be expressed on the cell surface to retain its native conformation, peptide libraries have been panned on whole cells and different positive selection protocols have been adopted to identify ligands for the receptor of interest. More recently, selections using whole cells have been directed at identifying ligands for unknown receptors with a particular property, for example tissue specificity or internalization. Protocols have been reported that improve the selection efficiency of specific ligands. An innovative approach to selecting ligands for receptors selectively expressed in the organ vasculature has been to inject a library into the circulation in mice. Harvesting peptides that distributed to different organs has identified ligands selectively homing to mouse brain or kidney blood vessels with no previous knowledge of the target receptor. Using the same in vivo panning approach, a library has been injected into the circulation of nude mice bearing human breast carcinoma xenograft, resulting in the identification of ligands for tumor-specific vascular markers. These peptides, previously shown to have high affinity for α(v) integrins, have been combined with a chemotherapeutic drug and shown to act more effectively than the drug alone in tumor-bearing mice.

Original languageEnglish
Pages (from-to)129-142
Number of pages14
JournalTumor Targeting
Volume4
Issue number3
Publication statusPublished - 1999

Fingerprint

Peptide Library
Ligands
Integrins
Peptides
Libraries
Blood Vessels
Neoplasms
Organ Specificity
Gene Targeting
Membrane Glycoproteins
Drug Delivery Systems
Heterografts
Nude Mice
Pharmaceutical Preparations
Cell Movement
Breast Neoplasms
Kidney
Brain

Keywords

  • Cell-surface receptors
  • Gene therapy
  • Phage display
  • Random peptide libraries
  • Targeting
  • Tumor targeting

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology

Cite this

Monaci, P., Bartoli, F., Di Zenzo, G., Nuzzo, M., & Urbanelli, L. (1999). Random peptide libraries for target definition. Tumor Targeting, 4(3), 129-142.

Random peptide libraries for target definition. / Monaci, P.; Bartoli, F.; Di Zenzo, G.; Nuzzo, M.; Urbanelli, L.

In: Tumor Targeting, Vol. 4, No. 3, 1999, p. 129-142.

Research output: Contribution to journalArticle

Monaci, P, Bartoli, F, Di Zenzo, G, Nuzzo, M & Urbanelli, L 1999, 'Random peptide libraries for target definition', Tumor Targeting, vol. 4, no. 3, pp. 129-142.
Monaci P, Bartoli F, Di Zenzo G, Nuzzo M, Urbanelli L. Random peptide libraries for target definition. Tumor Targeting. 1999;4(3):129-142.
Monaci, P. ; Bartoli, F. ; Di Zenzo, G. ; Nuzzo, M. ; Urbanelli, L. / Random peptide libraries for target definition. In: Tumor Targeting. 1999 ; Vol. 4, No. 3. pp. 129-142.
@article{48274eb61143491fa559a986fb5fccb0,
title = "Random peptide libraries for target definition",
abstract = "Several reports have shown that panning a random peptide library on a purified cellular receptor identified novel ligands for the target molecule. Many novel ligands for integrins, a class of trans-membrane glycoproteins involved in cell migration and tumor invasion, have been identified in this way. Peptides binding to integrins contained the RGD recognition motif flanked by residues which determine their specificity for differing integrins. Such peptides have been successfully used for targeting various gene and drug delivery vehicles to cell expressing the target integrin. When the target receptor needed to be expressed on the cell surface to retain its native conformation, peptide libraries have been panned on whole cells and different positive selection protocols have been adopted to identify ligands for the receptor of interest. More recently, selections using whole cells have been directed at identifying ligands for unknown receptors with a particular property, for example tissue specificity or internalization. Protocols have been reported that improve the selection efficiency of specific ligands. An innovative approach to selecting ligands for receptors selectively expressed in the organ vasculature has been to inject a library into the circulation in mice. Harvesting peptides that distributed to different organs has identified ligands selectively homing to mouse brain or kidney blood vessels with no previous knowledge of the target receptor. Using the same in vivo panning approach, a library has been injected into the circulation of nude mice bearing human breast carcinoma xenograft, resulting in the identification of ligands for tumor-specific vascular markers. These peptides, previously shown to have high affinity for α(v) integrins, have been combined with a chemotherapeutic drug and shown to act more effectively than the drug alone in tumor-bearing mice.",
keywords = "Cell-surface receptors, Gene therapy, Phage display, Random peptide libraries, Targeting, Tumor targeting",
author = "P. Monaci and F. Bartoli and {Di Zenzo}, G. and M. Nuzzo and L. Urbanelli",
year = "1999",
language = "English",
volume = "4",
pages = "129--142",
journal = "Tumor Targeting",
issn = "1351-8488",
publisher = "Stockton Press",
number = "3",

}

TY - JOUR

T1 - Random peptide libraries for target definition

AU - Monaci, P.

AU - Bartoli, F.

AU - Di Zenzo, G.

AU - Nuzzo, M.

AU - Urbanelli, L.

PY - 1999

Y1 - 1999

N2 - Several reports have shown that panning a random peptide library on a purified cellular receptor identified novel ligands for the target molecule. Many novel ligands for integrins, a class of trans-membrane glycoproteins involved in cell migration and tumor invasion, have been identified in this way. Peptides binding to integrins contained the RGD recognition motif flanked by residues which determine their specificity for differing integrins. Such peptides have been successfully used for targeting various gene and drug delivery vehicles to cell expressing the target integrin. When the target receptor needed to be expressed on the cell surface to retain its native conformation, peptide libraries have been panned on whole cells and different positive selection protocols have been adopted to identify ligands for the receptor of interest. More recently, selections using whole cells have been directed at identifying ligands for unknown receptors with a particular property, for example tissue specificity or internalization. Protocols have been reported that improve the selection efficiency of specific ligands. An innovative approach to selecting ligands for receptors selectively expressed in the organ vasculature has been to inject a library into the circulation in mice. Harvesting peptides that distributed to different organs has identified ligands selectively homing to mouse brain or kidney blood vessels with no previous knowledge of the target receptor. Using the same in vivo panning approach, a library has been injected into the circulation of nude mice bearing human breast carcinoma xenograft, resulting in the identification of ligands for tumor-specific vascular markers. These peptides, previously shown to have high affinity for α(v) integrins, have been combined with a chemotherapeutic drug and shown to act more effectively than the drug alone in tumor-bearing mice.

AB - Several reports have shown that panning a random peptide library on a purified cellular receptor identified novel ligands for the target molecule. Many novel ligands for integrins, a class of trans-membrane glycoproteins involved in cell migration and tumor invasion, have been identified in this way. Peptides binding to integrins contained the RGD recognition motif flanked by residues which determine their specificity for differing integrins. Such peptides have been successfully used for targeting various gene and drug delivery vehicles to cell expressing the target integrin. When the target receptor needed to be expressed on the cell surface to retain its native conformation, peptide libraries have been panned on whole cells and different positive selection protocols have been adopted to identify ligands for the receptor of interest. More recently, selections using whole cells have been directed at identifying ligands for unknown receptors with a particular property, for example tissue specificity or internalization. Protocols have been reported that improve the selection efficiency of specific ligands. An innovative approach to selecting ligands for receptors selectively expressed in the organ vasculature has been to inject a library into the circulation in mice. Harvesting peptides that distributed to different organs has identified ligands selectively homing to mouse brain or kidney blood vessels with no previous knowledge of the target receptor. Using the same in vivo panning approach, a library has been injected into the circulation of nude mice bearing human breast carcinoma xenograft, resulting in the identification of ligands for tumor-specific vascular markers. These peptides, previously shown to have high affinity for α(v) integrins, have been combined with a chemotherapeutic drug and shown to act more effectively than the drug alone in tumor-bearing mice.

KW - Cell-surface receptors

KW - Gene therapy

KW - Phage display

KW - Random peptide libraries

KW - Targeting

KW - Tumor targeting

UR - http://www.scopus.com/inward/record.url?scp=0032692546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032692546&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0032692546

VL - 4

SP - 129

EP - 142

JO - Tumor Targeting

JF - Tumor Targeting

SN - 1351-8488

IS - 3

ER -