Novel compounds are provided that bind to polo-like kinases through the polo-box domain. In certain embodiments, the novel compounds are PEGylated peptides. The PEGylated peptides in accordance with the invention demonstrate high PBD-binding affinity. In certain embodiments, the PEGylated peptides have also achieved activities in whole cell systems. The invention also provides compounds that bind polo-like kinases through the polo-box domain and possess reduced anionic charge. Further provided are methods of design and/or synthesis of the PEGylated peptides and methods of use thereof. The invention provides methods of use of the compounds and methods of synthesis of the compounds.

The present invention relates to a cross-linking agent for cross-linking an indole-structure-containing molecule to a desired molecule, the cross-linking agent containing, as an effective component, a radical compound having an N-oxy radical group and a group capable of bonding to the desired molecule.

In one aspect, the invention relates to compositions comprising stapled peptides, methods of making same, pharmaceutical compositions comprising same, and methods of treating various diseases, including, but not limited to, metabolic disorders such as diabetes, and cancers. The disclosed compounds comprise stapled peptides, including, but not limited to, stapled glucagon, axin, and p53 peptide homologues, which are useful as therapeutic agents for a variety of diseases as disclosed herein. The disclosed methods are useful in the preparation of a variety of stapled peptides, including stapled peptide homologues of glucagon, axin, and p53. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

A multifunctional chemical agents comprising functional agents Fn1, Fn2 and linkers, for the linchpin directed (LDM), protein directed (PDPM) modifications of proteins, and Fn1 accelerated kinetic labeling by Fn2.

Methods for generating cell-permeable hydrocarbon-stapled and/or stitched peptides lacking nonspecific membrane lytic properties and methods for using such peptides to target cellular proteins for experimental investigation and/or therapeutic benefit.

Provided is a method for solid phase synthesis of Etelcalcetide, comprising synthesizing Etelcalcetide backbone peptide resin, removing the side chain protecting group of Cys in the peptide chain, and then activating the sulfydryl group of the Cys side chain on the peptide resin with 2,2-dithiodipyridine and constructing a disulfide bond with L-Cys, such that a crude Etelcalcetide peptide is obtained by cleaving. The method does not require undergoing multi-step purification, the yield and purity of the obtained crude peptide are relatively high, and the total yield of the refined peptide after purification is greatly increased.

The present invention provides a manufacturing process for preparing a peptide, preferably a decapeptide, such as degarelix, by incorporating p-nitro-phenylalanin in the amino acid sequence preferably during stepwise solid phase synthesis, and converting these into the required amino acids Aph(Hor) and/or D-Aph(Cbm), preferably while attached to a solid phase. The invention further provides intermediates useful in the manufacturing process.

The invention relates to a novel amino acid having a tetrazine moiety and peptide or protein comprising the novel amino acid compounds. The invention also relates to a method of producing peptide or proteins comprising a tetrazine moiety and to the use of said peptide or proteins.

An unnatural amino acid may have a structure as shown in formula (1) or may be an enantiomer thereof:

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Such unnatural amino acid may be used, e.g., in recombinant proteins. A recombinant protein may contain such unnatural amino acid and a protein conjugate prepared from the recombinant protein. The unnatural amino acid can be simple and convenient to prepare, safe in nature, difficult to inactivate when inserted into a protein, and may have a high binding rate with a coupling moiety, and the obtained conjugate is higher in stability. The unnatural amino acid is applicable to numerous fields, especially in preparation of a recombinant protein or a recombinant protein conjugate.

The present invention provides a manufacturing process for preparing a peptide, preferably a decapeptide, such as degarelix, by incorporating p-nitro-phenylalanin in the amino acid sequence preferably during stepwise solid phase synthesis, and converting these into the required amino acids Aph(Hor) and/or D-Aph(Cbm), preferably while attached to a solid phase. The invention further provides intermediates useful in the manufacturing process.