A Systematic Study of the Sar in Second Generation Bradykinin Antagonists Leads to the Design of the First High Affinity Cyclic Peptide Antagonists

Peptides ◽  
1994 ◽  
pp. 381-383
Author(s):  
S. Chakravarty ◽  
B. J. Mavunkel ◽  
S. Lu ◽  
D. E. Wilkins ◽  
D. J. Kyle
Keyword(s):  
Systematic Study ◽  
Second Generation ◽  
Cyclic Peptide ◽  
High Affinity ◽  
Bradykinin Antagonists

scholarly journals Selection of high affinity ligands to hepatitis B core antigen from a phage-displayed cyclic peptide library

2002 ◽  
Vol 69 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Kok Lian Ho ◽  
Khatijah Yusoff ◽  
Heng Fong Seow ◽  
Wen Siang Tan
Keyword(s):  
Hepatitis B ◽  
Cyclic Peptide ◽  
Peptide Library ◽  
Core Antigen ◽  
Affinity Ligands ◽  
High Affinity ◽  
Hepatitis B Core Antigen ◽  
Selection Of

scholarly journals Adhesion Molecules in Melanoma—More than Just Superglue?

1996 ◽  
Vol 89 (7) ◽  
pp. 393-395 ◽  
Author(s):  
MD Mason ◽  
R Allman ◽  
M Quibell
Keyword(s):  
Signal Transduction ◽  
Cyclic Peptide ◽  
Αvβ3 Integrin ◽  
Cell Surface Molecules ◽  
Malignant Cells ◽  
Cell Behaviour ◽  
Surface Molecules ◽  
High Affinity ◽  
Natural Ligands ◽  
Integrin Family

Malignant melanoma is increasing in incidence, and, though early lesions are readily treatable, systemic therapy for metastatic disease remains disappointing. Integrins are a family of cell-surface molecules that mediate adhesion between the cell and the extracellular matrix. One member of the integrin family, the αvβ3 integrin, is associated with progression of melanomas, in that the most malignant cells express the highest levels of αvβ3. Like many members of the integrin family, αvβ3 recognizes the sequence Arg-Gly-Asp (RGD) in its ligands, and other molecules that contain this sequence will compete with the natural ligands (such as vitronectin) for binding. There is growing evidence that integrins function as receptors for signal transduction, and that integrin-mediated signalling can affect cell behaviour and even cell survival. Under certain circumstances, loss of integrin-mediated signalling will induce apoptosis, or programmed cell death, and we have demonstrated that melanoma cells treated with a cyclic peptide with high affinity for the αvβ3 integrin will undergo apoptosis within three days. This mechanism might be exploited therapeutically.

Cyclic, Cell-Penetrating Peptides Tailor-Made for the Creation of Peptide Libraries with Intrinsic Cell Permeability

2020 ◽  
Author(s):  
Nicolas A. Abrigo ◽  
Kara Dods ◽  
Koushambi Mitra ◽  
Kaylee Newcomb ◽  
Anthony Le ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Cell Penetrating Peptides ◽  
Peptide Libraries ◽  
Cell Permeability ◽  
Side Chain ◽  
High Affinity ◽  
Cell Penetrating ◽  
The Creation ◽  
Intracellular Targets ◽  
Macrocyclic Peptide

<p>The discovery of high-affinity peptides to many intracellular targets has become feasible through the development of diverse macrocyclic peptide libraries. But lack of cell permeability is a key feature hampering the use of these peptides as therapeutics. Here, we develop a set of small, cyclic peptide carriers that efficiently carry cargoes into the cytosol. These peptides are cyclized via side-chain alkylation, which makes them ideal for the creation of diverse mRNA or phage-displayed libraries with intrinsic cell permeability.</p>

Cyclic, Cell-Penetrating Peptides Tailor-Made for the Creation of Peptide Libraries with Intrinsic Cell Permeability

2020 ◽  
Author(s):  
Nicolas A. Abrigo ◽  
Kara Dods ◽  
Koushambi Mitra ◽  
Kaylee Newcomb ◽  
Anthony Le ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Cell Penetrating Peptides ◽  
Peptide Libraries ◽  
Cell Permeability ◽  
Side Chain ◽  
High Affinity ◽  
Cell Penetrating ◽  
The Creation ◽  
Intracellular Targets ◽  
Macrocyclic Peptide

<p>The discovery of high-affinity peptides to many intracellular targets has become feasible through the development of diverse macrocyclic peptide libraries. But lack of cell permeability is a key feature hampering the use of these peptides as therapeutics. Here, we develop a set of small, cyclic peptide carriers that efficiently carry cargoes into the cytosol. These peptides are cyclized via side-chain alkylation, which makes them ideal for the creation of diverse mRNA or phage-displayed libraries with intrinsic cell permeability.</p>

High affinity nonphosphorylated cyclic peptide inhibitors of Grb2-SH2/growth factor receptor interactions

2002 ◽  
pp. 568-570
Author(s):  
Ya-Qiu Long ◽  
Feng-Di T. Lung ◽  
Johannes H. Voigt ◽  
Zhu-Jun Yao ◽  
Terrence R. Burke ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cyclic Peptide ◽  
Growth Factor Receptor ◽  
Peptide Inhibitors ◽  
High Affinity ◽  
Receptor Interactions

scholarly journals Cyclic peptide unguisin A is an anion receptor with high affinity for phosphate and pyrophosphate

2017 ◽  
Vol 15 (14) ◽  
pp. 2962-2967 ◽  
Author(s):  
A. Daryl Ariawan ◽  
James E. A. Webb ◽  
Ethan N. W. Howe ◽  
Philip A. Gale ◽  
Pall Thordarson ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Cyclic Peptide ◽  
Anion Receptor ◽  
High Affinity ◽  
High Binding ◽  
Cyclic Heptapeptide ◽  
High Binding Affinity

Unguisin A (1) is a marine-derived, GABA-containing cyclic heptapeptide with a high binding affinity for phosphates.

Duplex–quadruplex motifs in a peculiar structural organization cooperatively contribute to thrombin binding of a DNA aptamer

2013 ◽  
Vol 69 (12) ◽  
pp. 2403-2411 ◽  
Author(s):  
Irene Russo Krauss ◽  
Andrea Pica ◽  
Antonello Merlino ◽  
Lelio Mazzarella ◽  
Filomena Sica
Keyword(s):  
Crystal Structure ◽  
Structural Study ◽  
Structural Organization ◽  
Second Generation ◽  
Dna Aptamer ◽  
High Affinity ◽  
G Quadruplex ◽  
And Control ◽  
Very High

Potent second-generation thrombin aptamers adopt a duplex–quadruplex bimodular folding and recognize thrombin exosite II with very high affinity and specificity. A sound model of these oligonucleotides, either free or in complex with thrombin, is not yet available. Here, a structural study of one of these aptamers, HD22-27mer, is presented. The crystal structure of this aptamer in complex with thrombin displays a novel architecture in which the helical stem is enchained to a pseudo-G-quadruplex. The results also underline the role of the residues that join the duplex and quadruplex motifs and control their recruitment in thrombin binding.

scholarly journals Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side

2017 ◽  
Vol 91 (10) ◽  
Author(s):  
Kuan-Hung Lin ◽  
Akbar Ali ◽  
Linah Rusere ◽  
Djade I. Soumana ◽  
Nese Kurt Yilmaz ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Protease Inhibitors ◽  
Active Site ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Content Type ◽  
Direct Acting Antiviral ◽  
High Affinity ◽  
Direct Acting ◽  
Ns3 Protease

ABSTRACT The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein with high affinity for DENV protease. In this study, we designed a series of cyclic peptides interacting with both sides of the active site as inhibitors of dengue virus protease. The design was based on two aprotinin loops and aimed to leverage both key specific interactions of substrate sequences and the entropic advantage driving aprotinin's high affinity. By optimizing the cyclization linker, length, and amino acid sequence, the tightest cyclic peptide achieved a Ki value of 2.9 μM against DENV3 wild-type (WT) protease. These inhibitors provide proof of concept that both sides of DENV protease active site can be exploited to potentially achieve specificity and lower hydrophilicity in the design of inhibitors targeting DENV. IMPORTANCE Viruses of the flaviviral family, including DENV and Zika virus transmitted by Aedes aegypti, continue to be a threat to global health by causing major outbreaks in tropical and subtropical regions, with no available direct-acting antivirals for treatment. A better understanding of the molecular requirements for the design of potent and specific inhibitors against flaviviral proteins will contribute to the development of targeted therapies for infections by these viruses. The cyclic peptides reported here as DENV protease inhibitors provide novel scaffolds that enable exploiting the prime side of the protease active site, with the aim of achieving better specificity and lower hydrophilicity than those of current scaffolds in the design of antiflaviviral inhibitors.

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