Disclosed are compositions and method related to variants of SPINK2 that bind to targets other than an endogenous target of SPINK2. In one embodiment, a peptide is provided that comprises the amino acid sequence SEQ ID NO: 1. In further embodiments, an amino acid sequences encoded by nucleotide positions 4 to 42 and/or nucleotide positions 94 to 189 in the nucleotide sequence of SEQ ID NO: 14 flank the amino terminus and the carboxyl terminus, respectively, of the amino acid sequence. In another embodiment, a peptide is provided that comprises an amino acid sequence derived from the amino acid sequence of SEQ ID NO: 1 in which a conservative substitution, deletion, addition and/or insertion of 1 to 5 (inclusive) amino acids has occurred at amino acids other than the 1st Xaa to the 12th Xaa counting from the amino terminus.

The present invention provides stapled polypeptides of the Formulae (I) and (VI):

##STR00001##

and salts thereof; wherein the groups ; R.sup.1a, R.sup.1b, R.sup.1c, R.sup.2a, R.sup.3a, R.sup.2b, R.sup.3b, R.sup.4a, R.sup.4b, R.sub.A, R.sub.Z, L.sub.1a, L.sub.1b, L.sub.2, L.sub.3, X.sup.AA, v, w, p, m, s, n, t, and q are as defined herein. The present invention further provides methods of preparing the inventive stapled polypeptides from unstapled polypeptide precursors. The present invention further provides pharmaceutical compositions comprising a stapled polypeptide of Formula (I) or (VI), and methods of using the stapled peptides. The present invention also provides modifications of the staples post ring closing metathesis.

The present invention provides stapled polypeptides of the Formulae (I) and (VI):

##STR00001##

and salts thereof; wherein the groups ; R.sup.1a, R.sup.1b, R.sup.1c, R.sup.2a, R.sup.3a, R.sup.2b, R.sup.3b, R.sup.4a, R.sup.4b, R.sub.A, R.sub.Z, L.sub.1a, L.sub.1b, L.sub.2, L.sub.3, X.sup.AA, v, w, p, m, s, n, t, and q are as defined herein. The present invention further provides methods of preparing the inventive stapled polypeptides from unstapled polypeptide precursors. The present invention further provides pharmaceutical compositions comprising a stapled polypeptide of Formula (I) or (VI), and methods of using the stapled peptides. The present invention also provides modifications of the staples post ring closing metathesis.

Synthesis of O-benzotriazole and O-imidazole synthons are described. Uses of synthons in synthesis of azapeptides and other peptidomimetics, azapeptides and other peptidomimetics synthesized from the synthons and uses of azapeptides and other peptidomimetics are also described.

An improved method for coupling amino acids into peptides or peptidomimetics is disclosed that includes the steps of combining an amino acid, a carbodiimide, an activator additive, and a base at less than 1 equivalent compared to the amino acid to be activated; and carrying out the activation and coupling at a temperature greater than 30° C.

An improved method for coupling amino acids into peptides or peptidomimetics is disclosed that includes the steps of combining an amino acid, a carbodiimide, an activator additive, and a base at less than 1 equivalent compared to the amino acid to be activated; and carrying out the activation and coupling at a temperature greater than 30° C.

Methods and system for solid phase peptide synthesis are provided. Solid phase peptide synthesis is a known process in which amino acid residues are added to peptides that have been immobilized on a solid support. New amino acid residues are added via a coupling reaction between an activated amino acid and an amino acid residue of the immobilized peptide. Amino acids may be activated using, e.g., a base and an activating agent. Certain inventive concepts, described herein, relate to methods and systems for the activation of amino acids. These systems and methods may allow for fewer side reactions and a higher yield compared to conventional activation techniques as well as the customization of the coupling reaction on a residue-by-residue basis without the need for costly and/or complex processes.

The present disclosure relates to lipoprotein complexes and lipoprotein populations and their use in the treatment and/or prevention of dyslipidemic diseases, disorders, and/or conditions. The disclosure further relates to recombinant expression of apolipoproteins, purification of apolipoproteins, and production of lipoprotein complexes using thermal cycling-based methods.

The present disclosure relates to lipoprotein complexes and lipoprotein populations and their use in the treatment and/or prevention of dyslipidemic diseases, disorders, and/or conditions. The disclosure further relates to recombinant expression of apolipoproteins, purification of apolipoproteins, and production of lipoprotein complexes using thermal cycling-based methods.

Disclosed is a solid phase method of synthesizing biomolecule-drug-conjugates. In particular, this invention relates to a solid phase method of synthesizing antibody-drug-conjugates (ADCs). This invention also relates to intermediate methods of producing immobilized, chemically modified biomolecules, e.g., antibodies.