The present invention includes a milk-derived polypeptide derivative, composition and its method for using. The milk-derived polypeptide together with its cell penetrating peptide derivatives can slow down body weight gain of mice induced by high-fat diet, reduce blood glucose, serum triglycerides and insulin levels, and improve insulin sensitivity and glucose tolerance. In addition, it can function to reduce body weight and blood glucose of already established obese mice model. Therefore, it has potentials to prepare drugs, health care products and food additives for preventing and treating obesity and its complications and other related diseases.

The present invention includes a milk-derived polypeptide derivative, composition and its method for using. The milk-derived polypeptide together with its cell penetrating peptide derivatives can slow down body weight gain of mice induced by high-fat diet, reduce blood glucose, serum triglycerides and insulin levels, and improve insulin sensitivity and glucose tolerance. In addition, it can function to reduce body weight and blood glucose of already established obese mice model. Therefore, it has potentials to prepare drugs, health care products and food additives for preventing and treating obesity and its complications and other related diseases.

Disclosed are a type of mitochondria-targeted polypeptides, the preparation method and the uses thereof. The polypeptide is abbreviated as MTP. The synthesis method of the present disclosure is simple, and the mitochondria-targeted polypeptide prepared by the method can specifically target the mitochondria of cells and are basically non-toxic to cells. In addition, these synthesized polypeptides demonstrate good cell-membrane-penetrating properties, and can conveniently undergo further multi-functional derivation and modification, thereby providing a potential delivery tool for the preparation of a mitochondria-targeted medicament.

Disclosed are a type of mitochondria-targeted polypeptides, the preparation method and the uses thereof. The polypeptide is abbreviated as MTP. The synthesis method of the present disclosure is simple, and the mitochondria-targeted polypeptide prepared by the method can specifically target the mitochondria of cells and are basically non-toxic to cells. In addition, these synthesized polypeptides demonstrate good cell-membrane-penetrating properties, and can conveniently undergo further multi-functional derivation and modification, thereby providing a potential delivery tool for the preparation of a mitochondria-targeted medicament.

The present invention relates to a method for preparing etelcalcetide hydrochloride (etelcalcetide HCL). A first peptide is de-protected and cleaved from a solid support by a first solution system, for obtaining a second peptide, followed by coupling an activated L-Cys-OH to the second peptide in the second solution system for forming a TFA salt of etelcalcetide that is not or hardly dissolved in the second solution system. After purification by column chromatography, the TFA salt of etelcalcetide can be converted to etelcalcetide HCL using a third solution system that excludes hydrogen chloride during a real-time monitoring salt exchange step. The present method provides a simplified process and the etelcalcetide HCL with high purity and yield, for being advantageously applied in mass production of etelcalcetide HCL.

The present invention relates to a method for preparing etelcalcetide hydrochloride (etelcalcetide HCL). A first peptide is de-protected and cleaved from a solid support by a first solution system, for obtaining a second peptide, followed by coupling an activated L-Cys-OH to the second peptide in the second solution system for forming a TFA salt of etelcalcetide that is not or hardly dissolved in the second solution system. After purification by column chromatography, the TFA salt of etelcalcetide can be converted to etelcalcetide HCL using a third solution system that excludes hydrogen chloride during a real-time monitoring salt exchange step. The present method provides a simplified process and the etelcalcetide HCL with high purity and yield, for being advantageously applied in mass production of etelcalcetide HCL.

The present disclosure provides engineered Class 1 Type I CRISPR-Cas (Cascade) systems that comprise multi-protein effector complexes, nucleoprotein complexes comprising Type I CRISPR-Cas subunit proteins and nucleic acid guides, polynucleotides encoding Type I CRISPR-Cas subunit proteins, and guide polynucleotides. Also, disclosed are methods for making and using the engineered Class 1 Type I CRISPR-Cas systems of the present invention.

The present disclosure provides engineered Class 1 Type I CRISPR-Cas (Cascade) systems that comprise multi-protein effector complexes, nucleoprotein complexes comprising Type I CRISPR-Cas subunit proteins and nucleic acid guides, polynucleotides encoding Type I CRISPR-Cas subunit proteins, and guide polynucleotides. Also, disclosed are methods for making and using the engineered Class 1 Type I CRISPR-Cas systems of the present invention.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.