CN-118598939-B - Kidney targeting polypeptide specifically bound with KIM-1 and application thereof in preparation of medicines for treating kidney diseases

Abstract

The invention provides a kidney targeting polypeptide specifically combined with KIM-1 and application thereof in preparing a medicament for treating kidney diseases, wherein the amino acid sequence of the kidney targeting polypeptide specifically combined with KIM-1 is shown as SEQ ID NO. 1. The targeting polypeptide can be specifically combined with an extracellular Ig V domain of kidney injury molecule-1 (KIM-1/HAVCR 1), so that the kidney targeting and treatment effects on injured kidneys are realized after kidney diseases such as kidney injury occur.

Inventors

• ZHENG LING
• HUANG KUN
• Xiao Yushuo
• CHEN HONG

Assignees

• 武汉大学

Dates

Publication Date

20260512

Application Date

20240507

Claims (6)

1. 1. The application of polypeptide with the amino acid sequence shown as SEQ ID NO.1 in preparing a medicament for treating acute kidney injury.
2. 2. The use according to claim 1, wherein the acute kidney injury is ischemia reperfusion-induced kidney injury.
3. 3. Use of a nucleic acid molecule encoding the polypeptide of claim 1 in the manufacture of a medicament for the treatment of acute kidney injury.
4. 4. Use of a recombinant expression vector comprising a nucleic acid molecule encoding the polypeptide of claim 1 in the manufacture of a medicament for treating acute kidney injury.
5. 5. Use of a host cell comprising the recombinant expression vector of claim 4 in the manufacture of a medicament for treating acute kidney injury.
6. 6. Use of a pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable targeted delivery vehicle for the manufacture of a medicament for the treatment of acute kidney injury.

Description

Kidney targeting polypeptide specifically bound with KIM-1 and application thereof in preparation of medicines for treating kidney diseases Technical Field The invention relates to the technical field of biological medicines, in particular to application of a kidney targeting polypeptide specifically combined with KIM-1 in preparation of a medicament for treating kidney diseases. Background Acute kidney injury (acute kidney injury, AKI) has high morbidity and mortality, and is a global significant public health problem. AKI is a clinical syndrome in which renal function drops sharply in a short period of time due to injury to renal structural or functional changes, and pathogenesis is complex. Acute kidney injury is more likely to occur in the elderly, chronic kidney disease patients, cardiovascular disease patients, diabetes patients, hypertension patients, etc., and about 1330 ten thousand AKI patients are present worldwide each year, of which 170 ten thousand die from AKI. Kidney injury molecule-1 (KIM-1/HAVCR 1) is a single transmembrane protein encoded by the HAVCR1 gene, which was originally found to be highly expressed during kidney injury and thus was considered a kidney injury marker. The extracellular structure of the KIM-1 protein comprises an immunoglobulin (IgV) domain and a mucin domain, the IgV domain being involved in the interaction of the extracellular matrix with other proteins. KIM-1 is only expressed in trace amounts or even absent in normal kidney tissue, but KIM-1 is expressed rapidly and in large amounts following AKI injury, producing high levels of KIM-1 protein at the cell membrane apical end of dedifferentiated proximal tubule cells. Several studies have shown that KIM-1 not only can be used as a biomarker for early detection of acute kidney injury, but its expression level can reflect the extent of AKI injury and prognostic indicators. Accurate diagnosis of early stage of AKI and timely intervention play a key role in prognosis of AKI patients. The current diagnostic criteria for AKI are not yet uniform, and current clinical diagnosis of AKI is overly dependent on serum creatinine levels, which are affected by a variety of factors, such as age, sex, muscle mass, diet, and the like. At the same time, elevated serum creatinine is often detected some time after kidney injury occurs, which may delay early diagnosis of AKI, missing the best early intervention opportunity. Although some drugs and therapeutic strategies are used to treat AKI, there is a lack of clear and effective treatments due to the variety of etiologies and courses of disease. Thus, the discovery of a diagnostic method and an effective therapeutic means with timeliness is critical for the treatment of acute kidney injury. Kidneys are one of the major metabolic organs in the body and play an important role in drug metabolism and excretion. The concentration of the drug in the kidneys is difficult to reach the level required for treatment due to the reabsorption of the drug in the tubular and the process of excreting urine from the body. In addition, the distribution of drugs in the kidneys is also affected by the renal structure and function. The tissue structure of kidney is special, including different parts of glomerulus, tubular and interstitial kidney, each part has different effect on the distribution and metabolism of medicine. The drug needs to pass through the tubular epithelial cells and tubular interstitium to enter the tubular lumen, and the permeability of the tubular epithelial cells, the presence of transport proteins that promote drug movement, and the biochemical environment of the tubular interstitium space all affect the distribution and metabolism of the drug. Thus, the distribution and metabolism of drugs in the kidneys is affected in many ways, making it difficult to enrich the kidneys to therapeutic concentrations. From the above, it is a key to find a harmless target capable of accumulating a drug in the kidney for effectively treating acute kidney injury. Therefore, there is a need to develop a targeting polypeptide for kidney targeting applications against acute kidney injury. Disclosure of Invention The invention solves the technical challenges of insufficient binding capacity of polypeptide to specific receptor of kidney and insufficient accumulation in damaged kidney. A targeting polypeptide for kidney targeting applications against acute kidney injury is provided, consisting of natural amino acid residues. The targeting polypeptide has the capability of specifically binding with a KIM-1 extracellular Ig V domain with high specificity in damaged kidneys, can be rapidly enriched in the damaged kidneys after kidney damage occurs, has a ratio of 3.43 in the kidneys to the livers, and has a polypeptide accumulation amount which is more than 3.5 times that of the undamaged kidneys. The innovation solves the technical problem that the targeted delivery of the medicine in the kidney can not be