Cyclooctene conjugates of therapeutic or diagnostic agents have improved aqueous solubility and can release the agents upon contact with a tetrazine-containing biomaterial. The cyclooctene conjugates provide site-selective delivery of agents at the location of the tetrazine-containing biomaterial in a subject. The compositions and methods have applications in the treatment of various diseases or conditions including cancer, tumor growths, and bacterial infections.

The present invention is to provide a method for producing a peptide containing an N-alkylamino acid, which comprises the following Steps (1) to (3). Step (1): a step of mixing an N-terminal protected amino acid or an N-terminal protected peptide with a carboxylic acid halide or a halogenated alkyl formate; Step (2): a step of mixing an amino acid or a peptide in which the N-terminal and the C-terminal are not protected with a trialkylsilylating agent; and Step (3): a step of mixing the product obtained in Step (1) with the product obtained in Step (2).

The present invention comprises compounds of Formula I. ##STR00001## wherein: Z.sub.4, Z.sub.7, Z.sub.9, Z.sub.11, Z.sub.22, Z.sub.23, Z.sub.26, Z.sub.30, Z.sub.34, Z.sub.35, p, m, n, q, and BRIDGE are defined in the specification. The invention also relates to pharmaceutical compositions and methods for use thereof. The novel compounds are useful for preventing, treating or ameliorating diseases and disorders, such as obesity, type 2 diabetes, the metabolic syndrome, insulin resistance, and dyslipidemia, among others.

A compound represented by formula (1):

##STR00001##

wherein b represents an integer of 1 to 5; X represents —NH— or —CO—; Z represents a group represented, for example, by formula (Z-1); R.sup.1 represents a hydrogen atom or (AB).sub.m; AB represents a particular amino acid residue, and when there is a plurality of ABs, each AB may be the same as or different from each other and ABs are bonded to each other via an amide bond; m represents an integer of 1 to 9; R.sup.2 represents a hydroxy group or (AC).sub.g; AC represents a particular amino acid residue, and when there is a plurality of ACs, each AC may be the same as or different from each other and ACs are bonded to each other via an amide bond; and g represents an integer of 1 to 9,
or a salt thereof.

A compound represented by formula (1):

##STR00001##

wherein R.sup.1 represents a hydrogen atom or a sulfonyl group; and Z represents a group represented by formula (Z-1),
or a salt thereof.

Provided are peptide analogs, pharmaceutical compositions comprising such compounds, and methods of treating cancer with such compounds.

The disclosure provides a method for preparing drug-linker MC-MMAF for antibody drug conjugates and intermediates therein. The preparation method of the present disclosure improves the reactivity of the N-terminal, thereby effectively controlling the occurrence of racemization; does not directly use the toxin MMAF, but uses fragmented peptides with lower toxicity, which minimizes the operational difficulty in scale-up production; no reverse phase is required and it is easy to prepare and operate.

The present invention is directed to novel heteroaryl sulfone-based conjugation handles of the formula: ##STR00001##
(wherein R.sup.1, R.sup.2, Het, D, E, X, Y, Z, m, n, p, q, r, s and t are as defined herein), methods for their preparation, their use in synthesizing antibody drug conjugates, and the resulting antibody drug conjugates made with components having heteroaryl sulfone-based conjugation handles.

The present invention comprises conjugates comprising a monoclonal antibody conjugated to a cyclic PYY peptide. The invention also relates to pharmaceutical compositions and methods for use thereof. The novel conjugates are useful for preventing, treating or ameliorating diseases and disorders disclosed herein.

Methods of treating aging related skin changes and of increasing skin thickness with topical administration of N-acyldipeptide derivatives are described. Compositions comprising N-acyldipeptide derivatives, are therapeutically effective for increasing skin thickness, and for treating extrinsic and intrinsic aging and aging related skin changes, such as fine lines, wrinkles, photoaging, hyperpigmentation, laxity, age spots, lentigines, mottled skin, and cellulite.