Abstract

Anticancer peptides (ACPs) are polycationic amphiphiles capable of preferentially killing a widespectrum of cancer cells relative to non-cancerous cells. Their primary mode of action is aninteraction with the cell membrane and subsequent activation of lytic effects, however it remainscontroversial the exact mechanism responsible for this mode of action. It has in previous studies been shown that utilizing zeta potential analyses it was possible to demonstrate the interaction of a small anticancer peptide with membrane modelsystems and cancer cells. Electrostatic interactions have a pivotal role in the cell killing processand in contrast to the AMPs action cell death occurs without achieving full neutralization of themembrane charge. The advent of microarray technology has revolutionized the search for genes that are differentially expressed across a range of cell types or experimental conditions. Traditional clustering methods, such as hierarchical clustering, are often difficult to deploy effectively since genes rarely exhibit similar expression pattern across a wide range of conditions. Web-enabled service called GEMS (Gene Expression Mining Server) for biclustering microarray data where Users may upload expression data and specify a set of criteria.GEMS performs bicluster mining based on a Gibbs sampling paradigm. Here, in Biogenea we have for the first time discovered an Anticancer Peptide SVS-1 multipharmacophore with an ini silico evaluated Efficacy in Preceding Membrane Neutralization using a web server for biclustering analysis of expression data.

Abstract

Although strong binding interactions between protein receptor and ligand do not require the participation of a large number of amino acids in either site, short peptide chains are generally poor at recreating the types of protein-protein interactions which take place during cell recognition and signalling process, probably because their flexible backbones prevent the side chains from forming sufficiently rigid and stable epitopes, which can take part in binding with the desired strength and specificity. In a recently-reported Research and Scientific Project, it was shown that a proto-epitope containing F, R and S amino acids has the ability to down-regulate TNF secretion by macrophages. Here, in Biogenea Pharmaceuticals Ltd we discovered for the first time the GENEA-Bicytonafer-2889. A Rational Designed and Optimised Bioactive Cyclic mimetic-Peptide Pharmacophore for the Generation of a Down-Regulator of TNF Secretion by Investigating Drug-Target Association and Dissociation Mechanisms Using Metadynamics-Based Algorithms.

Abstract

Interaction of polycystin-1 (PC1) and Gα12 is important for development of kidney cysts in autosomal dominant polycystic idney disease (ADPKD). The integrity of cell polarity and cell-cell adhesions (mainly E-cadherin-mediated adherens junction) is altered in the renal epithelial cells of ADPKD. However, the key signaling pathway for this alteration is not fully understood. Madin-Darby canine kidney (MDCK) cells maintain the normal integrity of epithelial cell polarity and adherens junctions. In other predicting model achieved an MCC of 0.915 and a sensitivity of 87.9% at the specificity level of 99.8% for 10-fold cross-validation test, and achieved an MCC of 0.895 and a sensitivity of 95.7% at the specificity level of 95.4% for independent set test. Here, in Biogenea Pharmaceuticals Ltd we discovered for the first time the GENEA-PolyGadherin-76112. A Rationally designed of Polycystin-1 and Gα12 poly-mimic pharmacophoric agents for the potential and future drug-based regulation of the cleavage of E-cadherin in kidney epithelial cells utilizing computer-aided Predicting netResearch and a BiogenetoligandorolTM based Scientific Project of drug-enzyme interaction on machine learning method

Abstract

Stimulating an immune response against cancer with the use of vaccines remainsa challenge. We hypothesized that combining a melanoma vaccine with interleukin-2, an immuneactivating agent, could improve outcomes. In a previous phase 2 Research Scientific Project, patients with metastaticmelanoma receiving high-dose interleukin-2 plus the gp100:209–217(210M) peptide vaccine hada higher rate of response than the rate that is expected among patients who are treated withinterleukin-2 alone. We here, present an evolutionary algorithm that works in conjunction with existing open-source software to automatically optimize candidate ligands for predicted binding affinity and other druglike properties. We used the rules of click chemistry to guide optimization, greatly enhancing synthesizability. Here, we have for the first time disxovered a computer simulated gp100 Peptide mimic designed pharmacophore as a Vaccine-like and Interleukin-2 superagonist in Patients withAdvanced Melanoma using an Improved Algorithm for Chemically Tractable, Semi-Automated Protein Inhibitor Design.

Abstract

Saint Louis encephalitis virus, a member of the $aviviridae subgroup, is a culex mosquito-borne pathogen. Despite severe epidemic outbreaks on several occasions, not much progress has been made with regard to an epitope-based vaccine designed for Saint Louis encephalitis virus. Covalent binding is an important mechanism for many drugs to gain its function. Computational algorithms to model this chemical event and extended it to a web server have been previously generated. The CovalentDock Cloud provides a simple yet user-friendly web interface to perform covalent docking experiments and analysis online. The web server accepts the structures of both the ligand and the receptor uploaded by the user or retrieved from online databases with valid access id. It identifies the potential covalent binding patterns, carries out the covalent docking experiments and provides visualization of the result for user analysis. Here, in Biogenea we have discovered for the first time a Computational Assay to Design an Epitope-Based Peptide Vaccine Mimo-Peptidic Hyper-Agonist with Mimetic PharmaScaffold chemical agents comprising vaccine like properties Against Saint Louis Encephalitis Virus. These novel hyperstructures were generated by Using the BiogenetoligandorolTM AND the CovalentDock Cloud: a web server for automated covalent docking.

Abstract

Vitiligo is a skin disorder characterized by selective melanocyte destruction and concomitant appearance of depigmented macules that over time enlarge, coalesce, and form patches. It has been suggested that vitiligo is, at least in part, caused by autoimmune responses mediated by cytotoxic T cells against melanocytes, causing depigmentation Immune responses contribute to the pathogenesis of vitiligo and target melanoma sometimes associated with vitiligo-like depigmentation in some melanoma patients. It has been perviously reported that the tyrosinase autoantigen was immunorecognized with the same molecular pattern by sera from vitiligo and melanoma patients. Five autoantigen peptides was found to compose the immunodominant antityrosinase response: aa95-104FMGFNCGNCK; aa175-182 LFVWMHYY; aa176-190FVWMHYYVSMDALLG; aa222-236IQKLTGDENFTIPYW, and aa233-247IPYWDWRDAEKCDIC. Synergistic therapies for the treatment of vitiligo are provided. The major therapies for the treatment of vitiligo a pigmentary disorder characterized by patchy depigmentation of skin are Psoralens plus UV-A, steroids, basic fibroblast growth factor (bFGF) peptide location or surgical procedures. Psoralens plus UV-A is effective in about 50% of cases, steroids are limitedly effective only in fast spreading cases of vitiligo and often reoccurs on stoppage of treatment. Surgical treatment is the last resort for vitiligo therapy, when all other therapies failed. It is limitedly effective. Basic fibroblast growth factor peptide(s) location was developed as a new mode therapy for the treatment of vitiligo. Therefore, SEQ ID NO: 01 VPHIPPN, SEQ ID NO: 02 MPPTQVS, SEQ ID NO: 03 QMHPWPP, SEQ ID NO: 1 1 LPLTPLP, SEQ ID NO: 12 QLNVNHQARADQ, SEQ ID NO: 13 TSASTRPELHYP, SEQ ID NO: 14 TFLPHQMHPWPP peptides, modified peptides and antibody or antibody fragments inhibiting the activity of MIA and can be used for treating vitiligo by inducing re-pigmentation. Fragment-based lead discovery is a method used for finding lead compounds as part of the drug discovery process. In this science project we perfomed an in silico ChemoProteomic Prediction-Scan for the generation of Antigenic PatternLFA-3/IgG fusion polypeptide aa95-104FMGFNCGNCK; aa175-182 LFVWMHYY; aa176-190FVWMHYYVSMDALLG; aa222-236IQKLTGDENFTIPYW, and aa233-247IPYWDWRDAEKCDICmimetic pharmacophore on conserved Vitiligo post-trancripts domains.

Abstract

CartiGeneaTM by Biopharmaceuticals Ltd is an advanced therapy medicinal autologous service for use in ACI treatment. CartiGeneaTM is an autologous suspension of approximately 15,000 ex vivo expanded cartilage cells per microliter of combined medium for autologous use. The cells have been obtained by ex vivo expansion of chondrocytes isolated from a biopsy of the articular cartilage from the patient’s knee. Treatment with CartiGeneaTM comprises a two-step surgical procedure. In the first step a cartilage biopsy is obtained arthroscopically from healthy articular cartilage from a lesser weight bearing area of the patient’s knee, approximately 4 weeks prior to implantation. Chondrocytes are isolated from the biopsy by enzymatic digestion, expanded in vitro, characterised and delivered as a suspension of 1 x 104 cells/μl for implantation in the same patient. During the second step of the procedure the expanded chondrocyte suspension is implanted in an open-knee surgery. The dosage of the cell suspension is defined as 0.8 to 1.5 million cells per cm2 defect size. Hence, depending on the defect size measured at biopsy procurement, 4 or 8 or 12 million cells are formulated into 1 or 2 or 3 vial(s) of 4 million cells/ 0.4 ml excipient.

The claimed indication for CartiGeneaTM is repair of single symptomatic cartilaginous defects of the femoral condyle of the knee (ICRS grade III or IV) in adults. By use of the proposed phantom method, dose reduction up to 75% was achievable, whereas for an intermediate level of iteration (level 4), the dose reduction ranged between 50% and 60%, depending on the tube voltage. For comparison, with the gradual adjustment of exposure settings, the corresponding dose reduction for the same level of iteration was about 35%. The proposed method provides rapid and efficient optimization of CT protocols and could be used as the first step in the optimization process.

Abstract

It has been previosuly reported that lipopeptides can be used to elicit cytotoxic T lymphocyte (CTL) responses against viral diseases and cancer. In previous scientific projects, it has also been determined that mono-palmitoylated peptides can enhance anti-tumor responses in the absence of adjuvant activity. To investigate whether di-palmitoylated peptides with TLR2 agonist activity are able to induce anti-tumor immunity, it was previously synthesized a di-palmitic acid-conjugated long peptide that contains a murine CTL epitope of HPV E749-57 (Pam2IDG). As a result we discovered for the first time the GENEA-Tollarepomir-5579, a Toll-like receptor agonist-conjugated peptide-mimetic pharmacophoric multi-targeted agent utilizing admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties based on a GRID-based three-dimensional pharmacophore on KLAPpharm within a novel BiogenetoligandorolTM basedKNIME-TDkit-CDK chemicalinformatic approach for conserved pharmacophore elucidation via a data mining analysis.

Abstract

Anticancer peptides (ACPs) are polycationic amphiphiles capable of preferentially killing a widespectrum of cancer cells relative to non-cancerous cells. Their primary mode of action is aninteraction with the cell membrane and subsequent activation of lytic effects, however it remainscontroversial the exact mechanism responsible for this mode of action. It has in previous studies been shown that utilizing zeta potential analyses it was possible to demonstrate the interaction of a small anticancer peptide with membrane modelsystems and cancer cells. Electrostatic interactions have a pivotal role in the cell killing processand in contrast to the AMPs action cell death occurs without achieving full neutralization of themembrane charge. The advent of microarray technology has revolutionized the search for genes that are differentially expressed across a range of cell types or experimental conditions. Traditional clustering methods, such as hierarchical clustering, are often difficult to deploy effectively since genes rarely exhibit similar expression pattern across a wide range of conditions. Web-enabled service called GEMS (Gene Expression Mining Server) for biclustering microarray data where Users may upload expression data and specify a set of criteria.GEMS performs bicluster mining based on a Gibbs sampling paradigm. Here, in Biogenea we have for the first time discovered an Anticancer Peptide SVS-1 multipharmacophore with an ini silico evaluated Efficacy in Preceding Membrane Neutralization using a web server for biclustering analysis of expression data.

Abstract

The ever-increasing number of tumor-associated antigens has provided a major stimulus for the development of therapeutic peptides vaccines. Tumor-associated peptides can induce high immune response rates and have been developed as vaccines for several types of solid tumors, and many are at various stages of clinical testing. MAGED4B, a melanoma antigen, is overexpressed in oral squamous cell carcinoma (OSCC) and this expression promotes proliferation and cell migration. In previous scientifc projects it has also been identified that 9 short peptides derived from MAGED4B protein are restricted in binding to the HLA subtypes common in the Asian population (HLA-A2, A11, and A24). As a result, we here discovered for the first time the GENEA-Immunomagetor-45700d utilizing the KNIME-BiogenetoligandorolTM-PASS-KNIME-based GA(M)E-QSAR-FIPSDock: a new molecular docking combinatorial clustering technique driven by fully informed swarm optimization algorithm and GA(M)E-QSAR: a novel, fully automatic genetic-algorithm-(meta)-ensembles approach for binary classification in ligand-based drug design based on Chemical and biological properties of frequent screening hits in predicting drug targets based on conserved binding pocket active MAGED4B protein domains.