The most common and most likely answer to this crossword clue is the 10 letter word ALIENATING
I've seen this crossword clue in The Daily Telegraph
A
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Buddy explains!

The straight part
We know that "Making an enemy of" is the straight/definition part of the clue. The straight part is often a synonym or definition, in this case making an enemy of = alienating.The cryptic/wordplay part
In cryptic crossword there's often an wordplay/cryptic part as well.This part involves a more complex hint, such as an anagram, homophone, hidden word, etc.
Sadly, We don't have an explanation for this specific crossword clue yet.
What does ALIENATING mean?
ALIENATING verb- To convey or transfer to another, as title, property, or right; to part voluntarily with ownership of.
- To estrange; to withdraw affections or attention from; to make indifferent or averse, where love or friendship before subsisted.
- Tending to alienate.