Disclosed are compounds, compositions, and methods involving cyclic peptides that can bind to KRAS (G12D) oncogenic protein. For example, disclosed are cyclic peptides that selectively bind KRAS (G12D) oncogenic protein. Also disclosed are methods of inhibiting KRAS (G12D) oncogenic protein in a cancer cell expressing KRAS (G12D) oncogenic protein. In some forms, the method comprises incubating the cancer cell with any one or more of the disclosed cyclic peptides. In some forms, the method comprises bringing into contact the cancer cell with any one or more of the disclosed cyclic peptides.

The present invention relates to an echinocandin analogue and a preparation method therefor. The compound can be used for preventing or treating fungal infection, or for preventing, stabilizing or inhibiting fungal growth or killing fungi. An exemplary compound is represented by formula I, wherein the definitions of R.sub.1, R.sub.2, R.sub.3 and G groups are as described in the description.

##STR00001##

The present invention relates to an echinocandin analogue and a preparation method therefor. The compound can be used for preventing or treating fungal infection, or for preventing, stabilizing or inhibiting fungal growth or killing fungi. An exemplary compound is represented by formula I, wherein the definitions of R.sub.1, R.sub.2, R.sub.3 and G groups are as described in the description.

##STR00001##

Provided are a cyclic peptide compound simulating a natural product structure- and a method for preparation thereof. The method is: the compound of formula I, a divalent palladium catalyst, and a silver salt undergoing an intramolecular arylation in a solvent under heating and stirring to construct a cyclic peptide, to generate the compound of formula II, in which the arylation sites are diverse, and can be extended to the side chain γ-position methyl or methylene of the majority hydrophobic amino acids to perform intramolecular arylation, thus overcoming the previous defect of the restriction of the types of selectable amino acids, and effectively constructing a novel aromatic ring-supported cyclic peptide compound. The aromatic ring support structure can form a novel 3D structure similar to a natural product, and provide a very favorable support for the subsequent construction of a cyclic peptide molecular library and high-throughput drug screening.

##STR00001##

The present inventors found cyclic peptide compounds that interact with Ras, and non-natural amino acids useful for the production of the cyclic peptide compounds. The inventors also found that the cyclic peptide compounds inhibit the binding between Ras and SOS. In addition, the inventors found specific non-natural amino acids contained in the cyclic peptide compounds and methods for production thereof.

Disclosed are compounds of Formula (I), or a pharmaceutically acceptable salt thereof: (I) wherein A, A.sup.1, A.sup.2, R.sup.1, R.sup.2 and R.sup.3 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.

##STR00001##

Embodiments of the present disclosure pertain to methods of selecting cyclic peptides that bind to a target by transforming a phage display library with a plurality of nucleic acids into bacterial host cells, where the nucleic acids include phage coat protein genes with a combinatorial region that encodes at least one cysteine and at least one non-canonical amino acid. The transformation results in the production of phage particles with phage coat proteins where the cysteine and the non-canonical amino acid couple to one another to form a cyclic peptide library. Phage particles are then screened against the desired target to select bound cyclic peptides. Amino acid sequences of the selected cyclic peptides are then identified. Additional embodiments pertain to methods of constructing a phage display library that encodes the cyclic peptides. Further embodiments of the present disclosure pertain to the produced cyclic peptides, phage display libraries and phage particles.

Embodiments of the present disclosure pertain to methods of selecting cyclic peptides that bind to a target by transforming a phage display library with a plurality of nucleic acids into bacterial host cells, where the nucleic acids include phage coat protein genes with a combinatorial region that encodes at least one cysteine and at least one non-canonical amino acid. The transformation results in the production of phage particles with phage coat proteins where the cysteine and the non-canonical amino acid couple to one another to form a cyclic peptide library. Phage particles are then screened against the desired target to select bound cyclic peptides. Amino acid sequences of the selected cyclic peptides are then identified. Additional embodiments pertain to methods of constructing a phage display library that encodes the cyclic peptides. Further embodiments of the present disclosure pertain to the produced cyclic peptides, phage display libraries and phage particles.

Template-fixed β-hairpin peptidomimetics of the general formula

##STR00001##

wherein Z is a template-fixed chain of 8 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly or Pro or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have agonizing or antagonizing activity against urotensin II or show inhibition of the STAT6/NCoA-1 interaction and can be used for preventing or treating diseases or disorders related to urotensin II, STAT6 and NCoA-1.

These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

Template-fixed β-hairpin peptidomimetics of the general formula

##STR00001##

wherein Z is a template-fixed chain of 8 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly or Pro or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have agonizing or antagonizing activity against urotensin II or show inhibition of the STAT6/NCoA-1 interaction and can be used for preventing or treating diseases or disorders related to urotensin II, STAT6 and NCoA-1.

These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.