The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions.

The disclosure describes compounds of Formula Ia, which in non-limiting aspects contain an asialoglycoprotein receptor (ASGPR) binding moiety and an anti-.sub.1AR binding moiety. Compounds of Formula Ia are useful in preventing, treating, and/or ameliorating heart failure in a subject when administered in therapeutically effective amounts.

The disclosure describes compounds of Formula Ia, which in non-limiting aspects contain an asialoglycoprotein receptor (ASGPR) binding moiety and an anti-.sub.1AR binding moiety. Compounds of Formula Ia are useful in preventing, treating, and/or ameliorating heart failure in a subject when administered in therapeutically effective amounts.

Reactions of 1,3-dipole-functional (e.g., azide-functional) platinum(IV) compounds with cyclic alkynes under conditions effective for a cycloaddition reaction to form a heterocyclic compound are disclosed herein. In certain embodiments, the conditions effective for the cycloaddition reaction to form the heterocyclic compound includes the substantial absence of added catalyst (e.g., copper catalyst).

The present invention relates to a cycloaddition process comprising the step of reacting a halogenated aliphatic 1,3-dipole compound with a (hetero)cycloalkyne according to Formula (1): Preferably, the (hetero)cycloalkyne according to Formula (1) is a (hetero)cyclooctyne. The invention also relates to the cycloaddition products obtainable by the process according to the invention. The invention further relates to halogenated aliphatic 1,3-dipole compounds, in particular to halogenated aliphatic 1,3-dipole compounds comprising N-acetylgalactosamine-UDP (GalNAc-UDP), and to halogenated 1,3-dipole compounds comprising (peracylated) N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), N-acetylmannosamine (ManNAc) and N-acetyl neuraminic acid (NeuNAc).

##STR00001##

A process is provided, comprising reacting a (hetero)aryl 1,3-dipole compound with a (hetero)cycloalkyne, wherein the (hetero)aryl 1,3-dipole compound comprises a 1,3-dipole functional group bonded to a (hetero)aryl group, and wherein the (hetero)aryl 1,3-dipole compound is a (hetero)aryl azide or a (hetero)aryl diazo compound; wherein:

(i) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound comprises a substituent

(ii) the (hetero)aryl group of the (hetero)aryl 1,3-dipole compound is an electron-poor (hetero)aryl group

and wherein the (hetero)cycloalkyne is a (hetero)cyclooctyne or a (hetero)cyclononyne according to Formula (1). The invention also relates to the products obtainable by the process according to the invention.

The present invention relates to inhibitors of zinc-dependent histone deacetylases (HDACs) useful in the treatment of diseases or disorders associated with HDAC6, having a Formulae I or Formula II: ##STR00001## where R, L, X.sup.1, X.sup.2, X.sup.3, X.sup.4, X.sup.5, Y.sup.1, Y.sup.2, Y.sup.3, and Y.sup.4 are described herein.

The disclosure describes compounds of Formula Ia, which in non-limiting aspects contain an asialoglycoprotein receptor (ASGPR) binding moiety and an anti-.sub.1AR binding moiety. Compounds of Formula Ia are useful in preventing, treating, and/or ameliorating heart failure in a subject when administered in therapeutically effective amounts.

The disclosure describes compounds of Formula Ia, which in non-limiting aspects contain an asialoglycoprotein receptor (ASGPR) binding moiety and an anti-.sub.1AR binding moiety. Compounds of Formula Ia are useful in preventing, treating, and/or ameliorating heart failure in a subject when administered in therapeutically effective amounts.

The disclosure describes compounds of Formula Ia, which in non-limiting aspects contain an asialoglycoprotein receptor (ASGPR) binding moiety and an anti-.sub.1AR binding moiety. Compounds of Formula Ia are useful in preventing, treating, and/or ameliorating heart failure in a subject when administered in therapeutically effective amounts.