Glycomimetics for the inhibition and modulation of lectins.

Carbohydrates are essential mediators of many processes in health and disease. They regulate self-/non-self- discrimination, are key elements of cellular communication, cancer, infection and inflammation, and determine protein folding, function and life-times. Moreover, they are integral to the cellular envelope for microorganisms and participate in biofilm formation. These diverse functions of carbohydrates are mediated by carbohydrate-binding proteins, lectins, and the more the knowledge about the biology of these proteins is advancing, the more interfering with carbohydrate recognition becomes a viable option for the development of novel therapeutics. In this respect, small molecules mimicking this recognition process become more and more available either as tools for fostering our basic understanding of glycobiology or as therapeutics. In this review, we outline the general design principles of glycomimetic inhibitors (Section 2). This section is then followed by highlighting three approaches to interfere with lectin function, i.e. with carbohydrate-derived glycomimetics (Section 3.1), novel glycomimetic scaffolds (Section 3.2) and allosteric modulators (Section 3.3). We summarize recent advances in design and application of glycomimetics for various classes of lectins of mammalian, viral and bacterial origin. Besides highlighting design principles in general, we showcase defined cases in which glycomimetics have been advanced to clinical trials or marketed. Additionally, emerging applications of glycomimetics for targeted protein degradation and targeted delivery purposes are reviewed in Section 4.

Chemotherapy-Induced, Broadly Reactive Autoantibodies in a Colon Cancer Patient.

The link between cancer and autoimmunity is well-established. For example, increased levels of autoantibodies are frequently found in cancer patients, and autoimmune diseases are linked to an increased risk for certain neoplasms. However, the extent to which chemotherapy induces autoimmune reactions remains largely elusive. Here, we quantified immunoglobulin M (IgM) responses to various human tissues and the patient's tumor before and during adjuvanted chemotherapy (seven cycles of the FOLFIRI regimen (folinic acid/fluorouracil/irinotecan) plus cetuximab) of a patient with metastasized colon cancer. IgM levels against all investigated tissues increased shortly after the first cycle and were further boosted by cycles two and three. Autoimmune responses then decreased during cycles four to seven but remained above baseline levels for most tissues. Our findings suggest that chemotherapy can induce broadly reactive autoimmune responses. Monitoring self-reactive IgM responses during treatment may help alleviate autoimmunity-related adverse events.