Described is a labeling technique which can facilitate the metabolism in the liver after administration to patients without the reduction in the antibody function, thereby reducing accumulation of radionuclides in an organ such as the liver, and a modified antibody containing an IgG antibody and an IgG-binding peptide bound to the IgG antibody. The IgG-binding peptide has an amino acid sequence consisting of 13 to 17 amino acid residues, such as GPDCAYH(Xaa1)GELVWCTFH (SEQ ID NO: 2) wherein Xaa1 represents a lysine residue, a cysteine residue, an aspartic acid residue, a glutamic acid residue, 2-aminosuberic acid, or diaminopropionic acid, and a compound represented by the following formula (II-1) is linked at a position of the lysine residue via a modification linker to the N terminus of the IgG-binding peptide. ##STR00001##

Described are methods for preparing a deuterated aldehyde using with a photocatalyst and a hydrogen atom transfer agent in a H.sub.2O free solvent comprising D.sub.2O and an organic solvent under an inert gas. The methods may be used to convert a wide variety of aldehydes (e.g., aryl, alkyl, or alkenyl aldehydes) to C-1 deuterated aldehydes under mild reaction conditions.

Provided are a compound superior in a cytotoxic action on cancer cells, an action inducing degradation of BET protein in cancer cells, and an inhibitory action on the binding of BET protein and acetylated histone, and useful as an anticancer agent, a BET protein degradation inducer or a BET protein inhibitor. A compound represented by the following formula (I) ##STR00001##
wherein each symbol is as defined in the specification, or a pharmacologically acceptable salt thereof.

The present invention relates to treatments of diabetic macular edema (DME) and impaired visual acuity, comprising intravitreally administering the compound of formula (A) (or a pharmaceutically acceptable salt and/or solvate thereof): Formula (A).

##STR00001##

Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.

A bio-related substance bonded to a branched and degradable polyethylene glycol derivative that is degraded in the cells represented by the following formula (A):

##STR00001##

wherein each symbol is as defined in the present specification, is provided by the present invention.

A multi-arm, degradable polyethylene glycol derivative with a high molecular weight that does not cause vacuolation of cells is provided. A degradable polyethylene glycol derivative represented by the following formula (1):

##STR00001##

wherein n1 and n2 are each independently 45-950, W.sup.1 and W.sup.2 are each independently an oligopeptide of 2-47 residues, a1 and a2 are each independently 1-8, Q is a hydrocarbon chain having 2-12 carbon atoms and optionally containing an oxygen atom and/or a nitrogen atom, X.sup.1 and X.sup.2 are each independently a functional group capable of reacting with a bio-related substance, and L.sup.1, L.sup.2, L.sup.3, L.sup.4, L.sup.5 and L.sup.6 are each independently a divalent spacer.

An object of the present invention is to provide a method for producing a peptide with high efficiency, and a method for producing a peptide which comprises the following steps (1) and (2): (1) a step of mixing an N-protected amino acid or an N-protected peptide with a carboxylic acid halide represented by the formula (I)

##STR00001##

(wherein X represents a halogen atom,
R.sup.1, R.sup.2 and R.sup.3 each independently represent an aliphatic hydrocarbon group which may have a substituent, and a total number of the carbon atoms in R.sup.1, R.sup.2 and R.sup.3 is 3 to 40); and (2) a step of mixing the product obtained in the step (1) and a C-protected amino acid or a C-protected peptide
is provided.

A heterobifunctional monodisperse polyethylene glycol with two adjacent monodisperse polyethylene glycol side chains, in which a peptide linker is degraded by intracellular enzymes to release a drug slowly and effectively mask the hydrophobicity of the drug, and an antibody-drug conjugate in which the antibody and the drug are bound using same is provided. A heterobifunctional monodisperse polyethylene glycol represented by the formula (1):

##STR00001##

wherein each symbol in the formula (1) is as defined in the DESCRIPTION.

Described herein are methods of syntheses and therapeutic uses of covalently modified peptides and/or proteins. The covalently modified peptides and/or proteins allow for improved pharmaceutical properties of peptide and protein-based therapeutics.