D-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability,improved oral bioavailability,as well as high binding affinity and spe...D-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability,improved oral bioavailability,as well as high binding affinity and specificity.Recently,D-peptide drugs have been attracting increasing attention in both academic and industrial researches over recent years.One D-peptide etelcalcetide has even entered the market that targets the calcium(Ca2+)-sensing receptor(CaSR) to fight secondary hyperparathyroidism.Effective discovery and optimization of D-peptide ligands that can bind to various disease-related targets with high specificity and potency is of great importance for the development of D-peptide drugs.This review surveys the recent method development in this area especially the chemical protein synthesis-assisted high-throughput screening strategies for D-peptide ligands and their application in drug discovery.展开更多
Molecular imaging was developed from basic molecular recognition.It can visualize not only the expression levels of specific molecules in a living system but also specific biological processes,thus providing guidance ...Molecular imaging was developed from basic molecular recognition.It can visualize not only the expression levels of specific molecules in a living system but also specific biological processes,thus providing guidance for early detection and treatment of diseases.As a noninvasive method,imaging agents are one of the foundations of high spatial resolution imaging,and their sensitivity and specificity can be improved by coupling targeting ligands to imaging probes.Among the various targeting ligands(antibodies,aptamers,etc.),targeting peptides are widely used in various modalities of molecular imaging due to their high affinities toward the molecular target and their excellent physicochemical properties.In this review,we summarize the design concepts and methods of targeting peptides in molecular imaging,introduce the combination of targeting peptides and imaging probes in different imaging modalities(e.g.,fluorescence imaging,radionuclide imaging),and provide examples of their applications in bioimaging.Finally,the challenges and strategies for clinical translation and practical application of targeting peptide-based imaging reagents are briefly discussed.展开更多
The one-bead-one-compound （OBOC） combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immu...The one-bead-one-compound （OBOC） combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immunoglobulin E （IgE） epitopes of the major shellfish allergen tropomyosin. OBOC peptide libraries with 8-12 amino acid residues were screened with serum samples from patients with shellfish allergy for IgE mimotopes of tropomyosin. Twenty-five mimotopes were identified from the screening and their binding reactivity to tropomyosin-specific IgE was confirmed by peptide ELISA. These mimotopes could be divided into seven clusters based on sequence homology, and epitope mapping by EpiSearch of the clustered mimotopes was performed to characterize and confirm the validity of mimotopes. Five out of six of the predicted epitopes were found to overlap with previously identified epitopes of tropomyosin. To further confirm the mimicry potential of mimotopes, BALB/c mice were immunized with mimotopes conjugated to keyhole limpet hemocyanin and assayed for their capacity to induce tropomyosin-specific antibodies. BALB/c mice that received mimotope immunization were found to have an elevated level of tropomyosin-specific immunoglobulin G, but not mice that received an irrelevant mimotope. This study pioneers the successful application of the OBOC libraries using whole sera to screen and identify multiple shrimp allergen mimotopes and validates their mimicry potential using in vitro, in vivo, and in silico methods.展开更多
基金supported by the National Key R&D Program of China(No.2019YFA0706902)National Natural Science Foundation of China(Nos.U1732161 and 91753120)Science and Technological Fund of Anhui Province for Outstanding Youth(No.1808085J04)。
文摘D-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability,improved oral bioavailability,as well as high binding affinity and specificity.Recently,D-peptide drugs have been attracting increasing attention in both academic and industrial researches over recent years.One D-peptide etelcalcetide has even entered the market that targets the calcium(Ca2+)-sensing receptor(CaSR) to fight secondary hyperparathyroidism.Effective discovery and optimization of D-peptide ligands that can bind to various disease-related targets with high specificity and potency is of great importance for the development of D-peptide drugs.This review surveys the recent method development in this area especially the chemical protein synthesis-assisted high-throughput screening strategies for D-peptide ligands and their application in drug discovery.
基金support from Beijing Natural Science Foundation(No.2222029)National Natural Science Foundation of China(Nos.22322403 and 22074006)Beijing Institute of Technology Research Fund Program for Young Scholars.
文摘Molecular imaging was developed from basic molecular recognition.It can visualize not only the expression levels of specific molecules in a living system but also specific biological processes,thus providing guidance for early detection and treatment of diseases.As a noninvasive method,imaging agents are one of the foundations of high spatial resolution imaging,and their sensitivity and specificity can be improved by coupling targeting ligands to imaging probes.Among the various targeting ligands(antibodies,aptamers,etc.),targeting peptides are widely used in various modalities of molecular imaging due to their high affinities toward the molecular target and their excellent physicochemical properties.In this review,we summarize the design concepts and methods of targeting peptides in molecular imaging,introduce the combination of targeting peptides and imaging probes in different imaging modalities(e.g.,fluorescence imaging,radionuclide imaging),and provide examples of their applications in bioimaging.Finally,the challenges and strategies for clinical translation and practical application of targeting peptide-based imaging reagents are briefly discussed.
文摘The one-bead-one-compound （OBOC） combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immunoglobulin E （IgE） epitopes of the major shellfish allergen tropomyosin. OBOC peptide libraries with 8-12 amino acid residues were screened with serum samples from patients with shellfish allergy for IgE mimotopes of tropomyosin. Twenty-five mimotopes were identified from the screening and their binding reactivity to tropomyosin-specific IgE was confirmed by peptide ELISA. These mimotopes could be divided into seven clusters based on sequence homology, and epitope mapping by EpiSearch of the clustered mimotopes was performed to characterize and confirm the validity of mimotopes. Five out of six of the predicted epitopes were found to overlap with previously identified epitopes of tropomyosin. To further confirm the mimicry potential of mimotopes, BALB/c mice were immunized with mimotopes conjugated to keyhole limpet hemocyanin and assayed for their capacity to induce tropomyosin-specific antibodies. BALB/c mice that received mimotope immunization were found to have an elevated level of tropomyosin-specific immunoglobulin G, but not mice that received an irrelevant mimotope. This study pioneers the successful application of the OBOC libraries using whole sera to screen and identify multiple shrimp allergen mimotopes and validates their mimicry potential using in vitro, in vivo, and in silico methods.
